☆ 4.6 Review

Immune landscape and immunotherapy of hepatocellular carcinoma: focus on innate and adaptive immune cells

CLINICAL AND EXPERIMENTAL MEDICINE (2023)

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Article Gastroenterology & Hepatology

Multiomics identifies the link between intratumor steatosis and the exhausted tumor immune microenvironment in hepatocellular carcinoma

Hiroki Murai et al.

Summary: Through the analysis of molecular abnormalities and tumor immune microenvironment in nonviral hepatocellular carcinoma, we identified the link between intratumoral steatosis and immune-exhausted immunotherapy-susceptible microenvironment.

HEPATOLOGY (2023)

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Article Gastroenterology & Hepatology

Gut microbiota-derived short-chain fatty acids regulate group 3 innate lymphoid cells in HCC

Chupeng Hu et al.

Summary: This study found that reduced levels of Lactobacillus reuteri and short-chain fatty acids (SCFAs) were associated with hepatocellular carcinoma (HCC) development. Acetate reduced IL-17A production in hepatic ILC3s by inhibiting histone deacetylase activity. Tumor-infiltrating ILC3s correlated with prognosis in HCC patients, which may be mediated by acetate. Modifying bacteria, changing SCFAs, reducing IL-17A-producing ILC3 infiltration, and combining with immune checkpoint inhibitors may contribute to the clinical treatment of HCC.

HEPATOLOGY (2023)

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Review Oncology

Efficacy and security of tumor vaccines for hepatocellular carcinoma: a systemic review and meta-analysis of the last 2 decades

Cheng-Long Han et al.

Summary: The study evaluated the efficacy and security of tumor vaccines for hepatocellular carcinoma (HCC). The results showed that tumor vaccines, especially DC vaccine, are safe and worth exploring. DC vaccine had a higher objective response rate (ORR) and longer median overall survival (OS)/progression-free survival (PFS) compared to peptide vaccine. HBV-related HCC may benefit more from tumor vaccines. However, more high-quality prospective studies are needed to further validate the efficacy and safety of tumor vaccines.

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY (2023)

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Article Oncology

Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments

Shogo Kumagai et al.

Summary: In highly glycolytic tumors, regulatory T (Treg) cells have higher PD-1 expression compared to effector T cells. Under low-glucose conditions, Treg cells actively absorb lactic acid through monocarboxylate transporter 1 (MCT1), promoting the expression of PD-1, while PD-1 expression by effector T cells is dampened. PD-1 blockade invigorates PD-1-expressing Treg cells, resulting in treatment failure.

CANCER CELL (2022)

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Article Biochemistry & Molecular Biology

TM4SF5-mediated liver malignancy involves NK cell exhaustion-like phenotypes

Hyunseung Sun et al.

Summary: The study revealed that TM4SF5 signaling contributes to immune evasion during liver carcinogenesis by suppressing NK cell number and function. Inhibiting TM4SF5 can restore NK cell surveillance, reduce fibrotic and cancerous phenotypes, and prolong survival in liver cancer.

CELLULAR AND MOLECULAR LIFE SCIENCES (2022)

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Article Gastroenterology & Hepatology

MicroRNA-206 promotes the recruitment of CD8+ T cells by driving M1 polarisation of Kupffer cells

Ningning Liu et al.

Summary: The study revealed that M2 polarisation of Kupffer cells is a major contributor to hepatocellular carcinoma in AKT/Ras mice, while microRNA-206 prevents HCC by promoting M1 polarisation of Kupffer cells and enhancing recruitment of CD8(+) T cells, suggesting its potential use as an immunotherapeutic approach.

GUT (2022)

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Article Gastroenterology & Hepatology

Mucosal-associated invariant T-cell tumor infiltration predicts long-term survival in cholangiocarcinoma

Christine L. Zimmer et al.

Summary: The study found that MAIT cells were heterogenously lost from intrahepatic and perihilar cholangiocarcinoma tumors possibly in response to increased bacterial burden, while the residual intratumoral MAIT cells exhibited preserved receptor repertoire for interaction with tumor cells. The high presence of MAIT cells in the livers of iCCA patients predicted long-term survival and was associated with a favorable antitumor immune signature.

HEPATOLOGY (2022)

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Article Gastroenterology & Hepatology

Novel low-avidity glypican-3 specific CARTs resist exhaustion and mediate durable antitumor effects against HCC

Leidy D. Caraballo Galva et al.

Summary: This study developed new low-affinity monoclonal antibodies and low-avidity CARTs for HCC, demonstrating that low-avidity CARTs can resist exhaustion and maintain functions in solid tumors, generating durable antitumor effects.

HEPATOLOGY (2022)

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Article Gastroenterology & Hepatology

Hypoxia-driven immunosuppression by Treg and type-2 conventional dendritic cells in HCC

Sheena Suthen et al.

Summary: This study analyzed the immune landscapes of hypoxic regions in hepatocellular carcinoma (HCC) and identified enriched immune subsets, including regulatory T cells, M2 macrophages, and HLA-DRlo cDC2, in hypoxia-high tumor regions. In contrast, hypoxia-low tumor regions showed an abundance of active granzyme B-hi PD-1(lo) CD8(+) T cells, indicating a relatively active immune landscape. The up-regulation of cancer-associated genes in tumor tissues and immunosuppressive genes in tumor-infiltrating leukocytes supported a highly pro-tumorigenic network in hypoxic HCC.

HEPATOLOGY (2022)

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Article Gastroenterology & Hepatology

Reciprocal alterations in circulating and hepatic gamma-delta T cells in patients with primary biliary cholangitis

Sha Chen et al.

Summary: This study found that the number of circulating TCRγδ low-expressing subset cells was significantly decreased in patients with primary biliary cholangitis (PBC). These cells may migrate to the liver via the CXCR6-CXCL16 axis and be involved in the pathogenesis of PBC by increasing granzyme B (GZMB) production.

HEPATOLOGY INTERNATIONAL (2022)

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Article Biotechnology & Applied Microbiology

Therapeutic Efficacy of an Oncolytic Influenza Virus Carrying an Antibody Against Programmed Cell Death 1 in Hepatocellular Carcinoma

Guanglin Lei et al.

Summary: In this study, a novel oncolytic influenza virus (IV) carrying an antihuman PD-1 monoclonal antibody was engineered. The results showed that this virus exhibited selective cytotoxicity and activated T cells in vivo, leading to suppressed tumor growth and increased survival in a liver cancer mouse model. These findings suggest that the combination of oncolytic IVs expressing PD-1 inhibitors could be a promising approach for HCC virotherapy.

HUMAN GENE THERAPY (2022)

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Review Biochemistry & Molecular Biology

Innate Lymphoid Cells and Intestinal Inflammatory Disorders

Mingzhu Zheng et al.

Summary: Innate lymphoid cells (ILCs) are a population of lymphoid cells that do not express T cell or B cell antigen-specific receptors. They play a protective role against pathogens mainly at mucosal sites. ILCs mimic the functions of CD4 T helper (Th) subsets and are involved in different immune responses by expressing specific cytokines and transcription factors. They have been found to be important in intestinal inflammation and related disorders.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Gastroenterology & Hepatology

Inhibition of carnitine palmitoyltransferase 1A in hepatic stellate cells protects against fibrosis

Marcos F. Fondevila et al.

Summary: We found that the expression of CPT1A is elevated in HSCs of patients with fibrosis, and that CPT1A induces the activation of these cells. Inhibition of CPT1A can ameliorate fibrosis by preventing the activation of HSCs.

JOURNAL OF HEPATOLOGY (2022)

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Article Gastroenterology & Hepatology

Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma

Ann-Lii Cheng et al.

Summary: The study demonstrated that atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma patients led to improved survival outcomes. After updated analysis, atezolizumab plus bevacizumab maintained its position as the first-line treatment option for advanced hepatocellular carcinoma.

JOURNAL OF HEPATOLOGY (2022)

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Article Oncology

Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial

Thomas Yau et al.

Summary: First-line nivolumab treatment did not significantly improve overall survival compared with sorafenib in patients with advanced hepatocellular carcinoma, but clinical activity and a favorable safety profile were observed in some patients.

LANCET ONCOLOGY (2022)

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Article Gastroenterology & Hepatology

Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma

Jaekyung Cheon et al.

Summary: This study aimed to investigate the safety and efficacy of Atezolizumab plus bevacizumab in real settings for patients with advanced hepatocellular carcinoma. The results showed that Ate/Bev demonstrated real-life efficacy and safety in Korean patients, consistent with the phase III trial results, but showed unfavorable outcomes in patients with elevated NLR.

LIVER INTERNATIONAL (2022)

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Article Oncology

Integrating bulk and single-cell RNA sequencing reveals cellular heterogeneity and immune infiltration in hepatocellular carcinoma

Tingjie Wang et al.

Summary: The efficacy of immunotherapy in hepatocellular carcinoma (HCC) is hindered by the high degree of tumor heterogeneity and immunosuppressive microenvironment. This study reveals three subtypes of HCC with different immune characteristics and prognosis. Furthermore, a transcription factor BATF is identified to upregulate immunosuppressive genes, and a specific macrophage subtype is found to promote the formation of immunosuppressive T-cells.

MOLECULAR ONCOLOGY (2022)

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Review Oncology

Immunotherapies for hepatocellular carcinoma

Josep M. Llovet et al.

Summary: Liver cancer, specifically hepatocellular carcinoma (HCC), is the second leading cause of cancer-related death globally. Traditional treatments involve specific drugs, but the emergence of immune checkpoint inhibitors has revolutionized the management of HCC.

NATURE REVIEWS CLINICAL ONCOLOGY (2022)

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Article Cell Biology

Disrupting N-glycan expression on tumor cells boosts chimeric antigen receptor T cell efficacy against solid malignancies

Beatrice Greco et al.

Summary: In solid tumors, the expression of N-glycans on tumor cells is negatively correlated with the killing ability of CAR T cells. Inhibiting N-glycan synthesis enhances CAR T cell activity and reduces interference from the PD-1-PD-L1 axis. The combination of 2DG and CAR T cell therapy shows effectiveness against multiple carcinomas.

SCIENCE TRANSLATIONAL MEDICINE (2022)

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Article Oncology

Myeloid-derived suppressor cell infiltration is associated with a poor prognosis in patients with hepatocellular carcinoma

Takahiro Tomiyama et al.

Summary: The present study examined the clinicopathological features of myeloid-derived suppressor cell (MDSC) and CD8(+) T-cell infiltration in hepatocellular carcinoma (HCC) and investigated their associations with patient outcomes. The results showed that high MDSC infiltration was associated with poorer clinical outcomes in HCC patients. Furthermore, the combination of MDSC and CD8(+) T-cell status enabled further classification of patients based on their outcomes.

ONCOLOGY LETTERS (2022)

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Article Gastroenterology & Hepatology

Effect of camrelizumab plus transarterial chemoembolization on massive hepatocellular carcinoma

Sujing Zhang et al.

Summary: The combination of camrelizumab and transarterial chemoembolization (TACE) shows promising efficacy in treating patients with massive hepatocellular carcinoma (HCC), as it improves liver function and reduces adverse events significantly.

CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY (2022)

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Article Genetics & Heredity

Hepatocellular carcinoma patients with high circulating cytotoxic T cells and intra-tumoral immune signature benefit from pembrolizumab: results from a single-arm phase 2 trial

Jung Yong Hong et al.

Summary: This study comprehensively characterized the genomic properties of hepatocellular carcinoma (HCC) patients in response to pembrolizumab treatment. It identified that the infiltration of cytotoxic T cells, increased active circulating CD8+ T cells, and down-regulation of neutrophil-associated markers significantly contributed to the effectiveness of pembrolizumab therapy. Female gender, PD-L1 positivity, and low neutrophil-to-lymphocyte ratio (NLR) were also identified as contributing factors to pembrolizumab response.

GENOME MEDICINE (2022)

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Review Allergy

The ingenious mast cell: Contemporary insights into mast cell behavior and function

Joakim S. Dahlin et al.

Summary: Mast cells play a crucial role in maintaining homeostasis and surveillance of the human body, releasing various mediators that affect both immune and non-immune cells. Research using animal models has contributed to a better understanding of mast cell function in health and disease.

ALLERGY (2022)

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Review Oncology

Immunotherapies for hepatocellular carcinoma

Justin K. H. Liu et al.

Summary: Cases of hepatocellular carcinoma are rapidly rising, particularly in the Western world. Traditional treatment options are reserved for early stage patients, while recent scientific advances in cancer immunotherapy have brought new hope for advanced cases.

CANCER MEDICINE (2022)

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Article Chemistry, Multidisciplinary

Remodeling Tumor-Associated Neutrophils to Enhance Dendritic Cell-Based HCC Neoantigen Nano-Vaccine Efficiency

Yunhao Wang et al.

Summary: This study develops a novel immunotherapy strategy for hepatocellular carcinoma (HCC) by using an acidic/photo-sensitive dendritic cell-based neoantigen nano-vaccine. The nano-vaccine converts the tumor from an immunologically cold state to a hot state and enhances the immune response by remodeling tumor-associated neutrophils. The results show promising efficacy in tumor regression and prolonged survival time in mice.

ADVANCED SCIENCE (2022)

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Review Oncology

Harnessing Antitumor CD4+ T Cells for Cancer Immunotherapy

Myriam Ben Khelil et al.

Summary: CD4(+) T cells play a crucial role in antitumor immunity, either by promoting or suppressing cytotoxic T cell responses. This review highlights the role of CD4(+) T subsets within the tumor microenvironment and discusses the latest developments in modulating CD4(+) T responses for cancer immunotherapy and improving cancer strategies.

CANCERS (2022)

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Review Oncology

Glypican-3: A Novel and Promising Target for the Treatment of Hepatocellular Carcinoma

Xiufeng Zheng et al.

Summary: GPC3 is specifically up-regulated in hepatocellular carcinoma and has shown promising value in diagnosis and treatment. GPC3-based therapeutic methods such as vaccines, immunotoxins, and CAR T or NK cells have emerged with exciting results.

FRONTIERS IN ONCOLOGY (2022)

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Review Oncology

Research progress on dendritic cell vaccines in cancer immunotherapy

Jifeng Yu et al.

Summary: DC vaccines have shown promising results in the treatment of hematological malignancies, including AML and MDS. Different strategies have been explored, such as using mo-DCs and DCleu as the main types of DCs, and loading DCs with various cancer-related molecules to enhance efficacy. Additionally, combination with conventional chemotherapy, specific antibodies, and immune checkpoint-targeting therapies have been investigated to improve the outcomes of DC vaccination. Overall, significant progress has been made in the field of DC vaccine immunotherapy.

EXPERIMENTAL HEMATOLOGY & ONCOLOGY (2022)

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Article Gastroenterology & Hepatology

Nomogram for prediction of long-term survival with hepatocellular carcinoma based on NK cell counts

Lihua Yu et al.

Summary: The study highlights the importance of NK cell counts in predicting the overall survival of hepatocellular carcinoma patients.

ANNALS OF HEPATOLOGY (2022)

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Article Oncology

Tumor endothelial cell-induced CD8+ T-cell exhaustion via GPNMB in hepatocellular carcinoma

Yoshihiro Sakano et al.

Summary: The role of tumor endothelial cells (TECs) in tumor-infiltrating T cells in hepatocellular carcinoma (HCC) is still unknown. This study found that TECs induce T cell exhaustion in HCC via expression of glycoprotein nonmetastatic melanoma protein B (GPNMB), suggesting GPNMB as a potential therapeutic target in HCC.

CANCER SCIENCE (2022)

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Article Oncology

Exosomal circGSE1 promotes immune escape of hepatocellular carcinoma by inducing the expansion of regulatory T cells

Mingyao Huang et al.

Summary: Exosomal circGSE1 derived from hepatocellular carcinoma (HCC) cells promotes HCC progression by inducing expansion of regulatory T cells (Tregs) via the miR-324-5p/TGFBR1/Smad3 axis.

CANCER SCIENCE (2022)

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Review Biochemistry & Molecular Biology

Type I interferon-mediated tumor immunity and its role in immunotherapy

Renren Yu et al.

Summary: Type I interferons inhibit tumor growth directly and indirectly by acting upon tumor and immune cells, with evidence showing that enhancing both endo- and exogenously produced type I IFNs have a synergistic effect on anti-tumor immunity. Clinical trials are currently exploring new treatment strategies combining type I IFN inducers with ICBs, highlighting the importance of understanding the cellular sources and roles of type I IFNs in the immune regulation of the tumor microenvironment.

CELLULAR AND MOLECULAR LIFE SCIENCES (2022)

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Article Gastroenterology & Hepatology

Topological analysis of hepatocellular carcinoma tumour microenvironment based on imaging mass cytometry reveals cellular neighbourhood regulated reversely by macrophages with different ontogeny

Jianpeng Sheng et al.

Summary: This study identified different functional units of HCC TME using imaging mass cytometry, with a focus on the importance of Kupffer cells in immunotherapy for HCC.

GUT (2022)

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Article Oncology

Cabozantinib Enhances Anti-PD1 Activity and Elicits a Neutrophil-Based Immune Response in Hepatocellular Carcinoma

Roger Esteban-Fabro et al.

Summary: The combination of cabozantinib and anti-PD1 has shown enhanced antitumor immunity in the treatment of advanced hepatocellular carcinoma (HCC). The combination therapy increases immune cell infiltration, reduces regulatory T cell infiltration, and alters cell proportions in the blood. It is also associated with less aggressive tumor phenotypes in HCC patients.

CLINICAL CANCER RESEARCH (2022)

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Article Gastroenterology & Hepatology

Requirement of RORα for maintenance and antitumor immunity of liver-resident natural killer cells/ILC1s

Jiaxi Song et al.

Summary: This study reveals the critical role of ROR alpha in the maintenance and function of LrNK cells/ILC1s, providing insights into the potential value of harnessing their activity in the treatment of liver cancer.

HEPATOLOGY (2022)

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Article Pharmacology & Pharmacy

Gamma delta (?d) T cells in cancer immunotherapy; where it comes from, where it will go?

Jiechu Deng et al.

Summary: Cancer immunotherapy is an important approach in the treatment of cancer, and gamma delta T cells have shown great potential in this field. Gamma delta T cells can recognize a wide range of antigens, exert anti-tumor effects, and can be manipulated for therapeutic interventions. However, research on gamma delta T cells is still in its infancy and faces many challenges and limitations.

EUROPEAN JOURNAL OF PHARMACOLOGY (2022)

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Article Gastroenterology & Hepatology

CXCR2 inhibition enables NASH-HCC immunotherapy

Jack Leslie et al.

Summary: This study found that targeting neutrophils using a CXCR2 small molecule inhibitor can enhance the sensitivity of non-alcoholic steatohepatitis-associated hepatocellular carcinoma (NASH-HCC) to immune checkpoint inhibition therapy (ICI). The combination therapy can reprogram the tumor immune microenvironment, increase the number of anti-tumor immune cells, and improve treatment outcomes.

GUT (2022)

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Article Gastroenterology & Hepatology

Single-cell profiling of human CD127+ innate lymphoid cells reveals diverse immune phenotypes in hepatocellular carcinoma

Yuanlin He et al.

Summary: This study investigated the immune phenotypic characteristics of ILC cells and the role of B cells in the inflammatory differentiation of ILC2 cells in HCC. Dysregulation of ILC cells and enrichment of the ICOS+ ILC2a subset were found in HCC and correlated with poor prognosis. B cells were found to play a role in inflammatory differentiation of ILC2 cells through ICOSL signaling and increased IL-13 production. Targeting ICOS and HSP70 suppressed tumor growth and remodeled the immunosuppressive tumor microenvironment, providing a potential strategy for HCC immunotherapy.

HEPATOLOGY (2022)

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Article Biochemistry & Molecular Biology

A Low Dose of Pure Cannabidiol Is Sufficient to Stimulate the Cytotoxic Function of CIK Cells without Exerting the Downstream Mediators in Pancreatic Cancer Cells

Francesca Garofano et al.

Summary: Through studying the role of the cannabinoid system in cancer development, it has been found that cannabidiol can enhance the cytotoxicity of killer cells without any associated side effects. This combinatorial approach with immune system cells shows potential for clinical treatment of pancreatic cancer.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Oncology

Adaptive antitumor immune response stimulated by bio-nanoparticle based vaccine and checkpoint blockade

Xuewei Bai et al.

Summary: The study found that Aspartate beta-hydroxylase (ASPH) can upregulate the expression of PD-L1 on breast and liver tumor cells through the ASPH-MYC signaling cascade, leading to immune evasion. The combination of a lambda phage vaccine targeting ASPH and PD-1 inhibitors can effectively inhibit the growth and progression of TNBC and HCC, significantly improving the therapeutic effect.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2022)

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Article Immunology

Ly49E separates liver ILC1s into embryo-derived and postnatal subsets with different functions

Yawen Chen et al.

Summary: The study reveals the heterogeneity of liver ILC1s and demonstrates the dynamic changes that occur in ILC1 subsets from different origins during ontogeny. Ly49E(+) ILC1s originate from embryonic non-bone marrow hematopoietic progenitor cells and play a role in neonatal innate immunity, while Ly49E(-) ILC1s develop from bone marrow and extramedullary hematopoietic progenitor cells after birth and are involved in adult immune memory responses.

JOURNAL OF EXPERIMENTAL MEDICINE (2022)

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Article Gastroenterology & Hepatology

T-cell exhaustion and residency dynamics inform clinical outcomes in hepatocellular carcinoma

Maryam Barsch et al.

Summary: This study investigated the responses of exhausted and resident T cells in peripheral blood and tumor microenvironment of hepatocellular carcinoma (HCC) patients and their clinical relevance. The findings revealed heterogeneous populations of exhausted CD8+ T cells (TEX) in the tumor microenvironment. The enrichment of severely exhausted CD8 T cells expressing multiple immune checkpoints was associated with poor survival, while a subset of more functional and metabolically active CD103+ tissue-resident memory T cells (TRM) expressing fewer immune checkpoints and PD-1 showed better survival. The enrichment of TEX was independently associated with prognosis, regardless of disease stage, alpha-fetoprotein levels, or age. In addition, a higher baseline TRM/TEX ratio was associated with disease control in patients treated with anti-PD-1 therapy.

JOURNAL OF HEPATOLOGY (2022)

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Article Biotechnology & Applied Microbiology

Type I IFNs repolarized a CD169+macrophage population with anti-tumor potentials in hepatocellular carcinoma

Jing Liao et al.

Summary: Reprogramming macrophages to express CD169 using a low dose of IFN enhances their phagocytic and CD8+ T cell-activating capacities, inhibits hepatoma growth, and can be further improved by blocking PD-L1 expression on macrophages.

MOLECULAR THERAPY (2022)

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Article Biochemistry & Molecular Biology

Natural killer cell dysfunction in cancer and new strategies to utilize NK cell potential for cancer immunotherapy

Wanze Zhang et al.

Summary: The dysfunction of immune cells is closely related to tumor progression and poor prognosis. In the tumor microenvironment, immunosuppressive factors inhibit the effector functions of immune cells, promoting tumor progression and metastasis. Dysfunctional NK cells, with weakened proliferation capacity and reduced production of effector cytokines, have limited ability to kill malignant cells and inhibit tumor progression. Reversing the dysfunctional state of NK cells and enhancing their effector functions is a promising strategy in cancer immunotherapy.

MOLECULAR IMMUNOLOGY (2022)

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Review Oncology

Crosstalk between NK cells and hepatic stellate cells in liver fibrosis

Yang Zhang et al.

Summary: Liver fibrosis is a common pathological process in chronic liver diseases, which can progress to irreversible cirrhosis and cancer. Hepatic stellate cells are activated and produce collagen in response to liver injury, triggering the initiation and progression of fibrosis. Natural killer cells, as a key component of hepatic innate immunity, can alleviate fibrosis by killing activated hepatic stellate cells. Current antifibrotic interventions have improved fibrosis, but cannot halt its progression in the advanced stage. Understanding the interaction between natural killer cells and hepatic stellate cells may provide clues for the pathogenesis and potential therapies for advanced liver fibrosis.

MOLECULAR MEDICINE REPORTS (2022)

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Review Oncology

Neutrophil extracellular traps in cancer

Leonardo Cristinziano et al.

Summary: Neutrophils, in addition to their well-known functions in the acute phases of the immune response, play important roles in tumor initiation and progression through the release of various mediators. Neutrophil extracellular traps (NETs), composed of DNA and decorating proteins, not only trap and kill extracellular pathogens, but also have both pro-inflammatory and anti-inflammatory effects in cancer-related inflammation. This review focuses on the mechanisms underlying the emerging effects of NETs in cancer initiation and progression.

SEMINARS IN CANCER BIOLOGY (2022)

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Article Virology

Oncolytic therapy with vaccinia virus carrying IL-24 for hepatocellular carcinoma

Lili Deng et al.

Summary: In this study, a recombinant vaccinia virus, VG9-IL-24, was constructed, which selectively infected hepatocellular carcinoma cells and induced apoptosis, showing promising antitumor effects. Additionally, VG9-IL-24 blocked the cell cycle progression and suppressed tumor growth.

VIROLOGY JOURNAL (2022)

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Article Multidisciplinary Sciences

Characterisation and induction of tissue-resident gamma delta T-cells to target hepatocellular carcinoma

Nekisa Zakeri et al.

Summary: This study suggests that boosting T-cells with tissue-resident memory T-cells (T-RM) may improve the response to immunotherapy for advanced hepatocellular carcinoma (HCC). Higher frequencies of gamma delta T-cells, which exhibit tissue-residency and superior anti-tumour cytokine production, are associated with enhanced patient survival. Aminobisphosphonate-based expansion of V gamma 9V delta 2T cells can potentially replenish the depleted pool and enhance cytotoxic potential, making it a promising approach for HCC immunotherapy.

NATURE COMMUNICATIONS (2022)

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Article Multidisciplinary Sciences

Trajectory of immune evasion and cancer progression in hepatocellular carcinoma

Phuong H. D. Nguyen et al.

Summary: This study reveals extensive immune remodeling in hepatocellular carcinoma at different stages, indicating a progressive immune evasion of the tumor. The findings provide insights into potential interventions to reverse, prevent or limit the progression of the disease.

NATURE COMMUNICATIONS (2022)

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Article Oncology

IFNa Potentiates Anti-PD-1 Efficacy by Remodeling Glucose Metabolism in the Hepatocellular Carcinoma Microenvironment

Bo Hu et al.

Summary: The combination of IFN alpha and anti-PD-1-based immunotherapy enhanced antitumor activity in patients with unresectable HCC by reprogramming glucose metabolism within the tumor microenvironment and increasing cytotoxic capabilities of infiltrating CD8 + T cells. Additionally, tumor-infiltrating CD27 + CD8 + T cells may serve as a promising biomarker for stratifying patients for anti-PD-1 therapy.

CANCER DISCOVERY (2022)

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Article Multidisciplinary Sciences

The gut microbiome as mediator between diet and its impact on immune function

Huiqing Shi et al.

Summary: Dietary habits can impact inflammation in the human body, and the gut microbiome may play a mediating role in this interaction. This study found that a meat-based diet and high alcohol consumption were associated with higher concentrations of inflammatory biomarkers, while a prudent diet was associated with anti-inflammatory biomarkers. The study also revealed that the relationship between diet and immune function may be partially mediated by the gut microbiome.

SCIENTIFIC REPORTS (2022)

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Article Oncology

Combination Neoantigen-Based Dendritic Cell Vaccination and Adoptive T-Cell Transfer Induces Antitumor Responses Against Recurrence of Hepatocellular Carcinoma

Sui Peng et al.

Summary: This study demonstrates that personalized neoantigen-loaded immunotherapy as adjuvant treatment has the potential to reduce hepatocellular carcinoma recurrence after curative therapy, is feasible, and has a good safety profile.

CANCER IMMUNOLOGY RESEARCH (2022)

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Article Oncology

Myeloid-derived suppressor cells promote tumor growth and sorafenib resistance by inducing FGF1 upregulation and fibrosis

Xue Deng et al.

Summary: This study demonstrates that MDSCs contribute to tumor growth and sorafenib resistance through the upregulation of FGF1 and subsequent activation of CAF. The findings provide a novel mechanism for MDSC-driven HCC progression and sorafenib resistance.

NEOPLASIA (2022)

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Article Oncology

Efficacy and safety of camrelizumab plus apatinib during the perioperative period in resectable hepatocellular carcinoma: a single-arm, open label, phase II clinical trial

Yongxiang Xia et al.

Summary: Perioperative camrelizumab plus apatinib shows promising efficacy and manageable toxicity in patients with resectable HCC. DCs infiltration might be a predictive marker of response to camrelizumab and apatinib as well as patients' recurrence. ctDNA as a compose biomarker can predict pathological response and relapse. Abnormal glucose metabolism in patients with multifocal HCC may be related to different sensitivity of treatment in different lesions.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

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Article Oncology

Mitoribosomal defects aggravate liver cancer via aberrant glycolytic flux and T cell exhaustion

Byong-Sop Song et al.

Summary: Mitochondrial ribosomal protein dysfunction is associated with hepatocellular carcinoma progression and leads to an immunometabolic microenvironment favorable for cancer progression. Impaired mitoribosomal function promotes glucose partitioning toward glycolytic flux, lactate synthesis, and T cell exhaustion. This study provides insights into the critical role of mitoribosomes in regulating the immunometabolic characteristics of liver cancer.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

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Review Oncology

MicroRNAs/LncRNAs Modulate MDSCs in Tumor Microenvironment

Xiaocui Liu et al.

Summary: This article summarizes the regulation of miRNA/lncRNA on the differentiation, expansion, and immunosuppressive function of tumor MDSCs in the tumor microenvironment. The regulatory mechanisms of exosomal miRNA/lncRNA on tumor MDSCs are discussed, and the interaction of miRNA/lncRNA in modulating tumor MDSCs is also explored.

FRONTIERS IN ONCOLOGY (2022)

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Article Oncology

Hepatocellular carcinoma-infiltrating γδ T cells are functionally defected and allogenic Vδ2+ γδ T cell can be a promising complement

Wenjing He et al.

Summary: This study reported the dysfunctional features of γδ T cells in hepatocellular carcinoma (HCC) within the tumor microenvironment, providing scientific support for the use of allogeneic V delta 2(+) γδ T cells in HCC immunotherapy.

CLINICAL AND TRANSLATIONAL MEDICINE (2022)

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Article Chemistry, Medicinal

Oncolytic Vaccinia Virus Harboring Aphrocallistes vastus Lectin Inhibits the Growth of Hepatocellular Carcinoma Cells

Riqing Jiang et al.

Summary: The oncolytic vaccinia virus containing Aphrocallistes vastus lectin (oncoVV-AVL) has shown significant anti-tumor effects in hepatocellular carcinoma. The virus activates tumor immunity by upregulating type I interferon expression and enhances replication by inhibiting ISRE mediated viral defense response. Furthermore, the lectin regulates multiple signaling pathways to promote virus replication.

MARINE DRUGS (2022)

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Article Immunology

Human ILC3 Exert TRAIL-Mediated Cytotoxicity Towards Cancer Cells

Jana-Julia Siegler et al.

Summary: ILC3s are cytokine-producing lymphocytes that directly respond to tumor cells, leading to enhanced IFN-gamma release and TRAIL-dependent cytotoxicity against cancer cells. This suggests that ILC3s may play a role in anti-tumor immunity and could be further utilized for cancer therapies.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Oncology

Lenvatinib suppresses cancer stem-like cells in HCC by inhibiting FGFR1-3 signaling, but not FGFR4 signaling

Taku Shigesawa et al.

Summary: This study demonstrates that lenvatinib reduces CSCs in HCC by inhibiting FGFR1-3 signaling, while not affecting FGFR4 signaling. FGF2 and FGF19 may be involved in maintaining CSCs in HCC through FGFR1-3.

CARCINOGENESIS (2021)

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Article Gastroenterology & Hepatology

Intratumoral γδ T-Cell Infiltrates, Chemokine (C-C Motif) Ligand 4/Chemokine (C-C Motif) Ligand 5 Protein Expression and Survival in Patients With Hepatocellular Carcinoma

Na Zhao et al.

Summary: The study found an increased infiltration of gamma delta T cells in the tumor microenvironment of HCC patients, positively correlated with the expression of immune-related genes. Interaction between CCL4/CCL5 and their receptors CCR1/CCR5 may facilitate the recruitment of gamma delta T cells from peripheral blood or surrounding areas to tumor regions.

HEPATOLOGY (2021)

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Review Oncology

Cytotoxic CD8+T cells in cancer and cancer immunotherapy

Hans Raskov et al.

Summary: The functions and interactions between the innate and adaptive immune systems play a crucial role in anticancer immunity. Cytotoxic T cells with CD8 as the most effective effectors in the anticancer immune response form the basis of successful cancer immunotherapies. Advancements in genetically modified or synthetic receptors on cytotoxic T cells are being developed for future cancer treatment. Combinatory regimens may optimize treatment effects and reduce adverse events in cancer therapy.

BRITISH JOURNAL OF CANCER (2021)

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Article Immunology

Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer

Yan Xu et al.

Summary: The study focused on utilizing allogeneic V gamma 9V delta 2 T cells for tumor immunotherapy, developing a novel formula for expanding gamma delta T cells from healthy donors, and conducting clinical trials to prove the safety and efficacy of allogeneic V gamma 9V delta 2 T cells, showing promising results in late-stage cancer patients.

CELLULAR & MOLECULAR IMMUNOLOGY (2021)

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Article Biochemistry & Molecular Biology

Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma

Yunfan Sun et al.

Summary: This study showed that early-relapse hepatocellular carcinoma (HCC) tumors exhibit innate-like CD8(+) T cells with overexpression of KLRB1 (CD161) and a low cytotoxic state, unlike the exhausted state seen in primary HCC. These cells were associated with a worse prognosis. Additionally, potential immune evasion mechanisms were identified in recurrent tumor cells, which dampen dendritic cell antigen presentation and recruit innate-like CD8(+) T cells.

CELL (2021)

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Article Cell Biology

A recombinant influenza virus with a CTLA4-specific scFv inhibits tumor growth in a mouse model

Guang-Lin Lei et al.

Summary: Oncolytic viruses, especially influenza A virus, have shown promising results in cancer immunotherapy. By constructing a recombinant influenza virus expressing an immune checkpoint blockade agent targeting CTLA4, the study demonstrated high selectivity in killing hepatocellular carcinoma cells and improved survival in a mouse model, indicating the potential for further exploration in cancer therapy.

CELL BIOLOGY INTERNATIONAL (2021)

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Review Immunology

Immunobiology and immunotherapy of HCC: spotlight on innate and innate-like immune cells

Benjamin Ruf et al.

Summary: Immune-based therapies, particularly immune checkpoint inhibitors, have shown significant improvements in the treatment of hepatocellular carcinoma (HCC), but durable responses are limited to a subset of patients. Understanding the immunologic mechanisms shaping the unique tumor microenvironment of liver cancer is crucial for developing effective therapeutic strategies. Current research focuses on targeting immune cells within the liver to enhance the therapeutic potential of immunotherapeutic agents.

CELLULAR & MOLECULAR IMMUNOLOGY (2021)

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Article Oncology

Plasmacytoid dendritic cells recruited by HIF-1α/eADO/ADORA1 signaling induce immunosuppression in hepatocellular carcinoma

Li Pang et al.

Summary: This study found that the accumulation of pDCs in HCC patients is correlated with poor prognosis. Hypoxia-induced eADO enhances pDC recruitment into tumors via ADORA1, affecting the function of immune cells.

CANCER LETTERS (2021)

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Article Gastroenterology & Hepatology

Therapeutic efficacy of dendritic cell vaccine combined with programmed death 1 inhibitor for hepatocellular carcinoma

Chiao-Fang Teng et al.

Summary: The study showed that combining dendritic cell vaccine and PD-1 inhibitor as a therapeutic strategy for HCC significantly prolonged overall survival, reduced tumor volume, and increased cytotoxicity of T cells against cancer cells.

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY (2021)

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Review Oncology

CD155/TIGIT, a novel immune checkpoint in human cancers

Lu Liu et al.

Summary: CD155/T cell immunoreceptor with Ig and ITIM domains (TIGIT) is a novel type of immune checkpoint that inhibits the function of T and NK cells by transmitting immune signals through the inhibitory receptor TIGIT. This mechanism holds promise for further improving the application of immune checkpoint inhibitors in tumor therapy.

ONCOLOGY REPORTS (2021)

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Review Oncology

The Functional Crosstalk between Myeloid-Derived Suppressor Cells and Regulatory T Cells within the Immunosuppressive Tumor Microenvironment

Maximilian Haist et al.

Summary: Immunotherapy has shown benefits for advanced cancer patients, but many still do not respond to treatment. The accumulation of immunosuppressive cell populations like MDSC and Treg in the tumor microenvironment contributes to immune resistance and limits the effectiveness of immunotherapy.

CANCERS (2021)

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Review Oncology

Neutrophils in cancer carcinogenesis and metastasis

Shumin Xiong et al.

Summary: Research on the roles and mechanisms of neutrophils in cancer has been gaining attention, with controversial findings indicating the dual role of neutrophils in promoting and suppressing cancer. The diversity and plasticity of neutrophils allow them to adapt to different cancer microenvironments.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2021)

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Article Oncology

Hepatitis B-Induced IL8 Promotes Hepatocellular Carcinoma Venous Metastasis and Intrahepatic Treg Accumulation

Changlu Zhang et al.

Summary: The study identifies a HBV-induced IL8/CXCR1/TGF beta signaling cascade that suppresses antitumor immunity and enhances metastasis in HCC. This provides new potential targets for therapeutic intervention.

CANCER RESEARCH (2021)

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Article Oncology

Chronic restraint stress promotes the mobilization and recruitment of myeloid-derived suppressor cells through β-adrenergic-activated CXCL5-CXCR2-Erk signaling cascades

Mingyue Cao et al.

Summary: The study reveals that chronic restraint stress significantly promotes HCC growth and mobilizes MDSCs to spleen and tumor sites from bone marrow through enhancing CXCR2 and pErk1/2 expression. In addition, beta-adrenergic signaling cascade plays a crucial role in the mobilization and recruitment of MDSCs under chronic restraint stress.

INTERNATIONAL JOURNAL OF CANCER (2021)

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Review Biochemistry & Molecular Biology

Endoplasmic Reticulum Stress Signaling and the Pathogenesis of Hepatocarcinoma

Juncheng Wei et al.

Summary: Hepatocellular carcinoma is a major cause of cancer mortality globally, and its pathogenesis involves the interplay of ER stress and unfolded protein response. The liver's susceptibility to ER stress, due to its functions in protein synthesis and detoxification, may play a crucial role in HCC development and treatment response.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Cell Biology

Cancer-associated fibroblast-derived CXCL11 modulates hepatocellular carcinoma cell migration and tumor metastasis through the circUBAP2/miR-4756/IFIT1/3 axis

Gao Liu et al.

Summary: CAFs-derived cytokines can enhance hepatocellular carcinoma progression and metastasis by activating the circRNA-miRNA-mRNA axis in tumor cells, with CXCL11 playing a key role in this process.

CELL DEATH & DISEASE (2021)

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Article Multidisciplinary Sciences

Tumor methionine metabolism drives T-cell exhaustion in hepatocellular carcinoma

Man Hsin Hung et al.

Summary: The study reveals a correlation between T-cell exhaustion and overall survival in hepatocellular carcinoma patients, suggesting a link to oncogenic reprogramming of methionine metabolism. Reprogramming tumor methionine metabolism could be a potential therapeutic strategy to enhance HCC immunity.

NATURE COMMUNICATIONS (2021)

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Article Medicine, Research & Experimental

Endoplasmic reticulum stress promotes sorafenib resistance via miR-188-5p/hnRNPA2B1-mediated upregulation of PKM2 in hepatocellular carcinoma

Bei Zhou et al.

Summary: The study revealed that endoplasmic reticulum stress promotes sorafenib resistance in hepatocellular carcinoma via the upregulation of PKM2 through the miR-188-5p/hnRNPA2B1 pathway. Targeting this pathway and ER stress could be a potential strategy to overcome sorafenib resistance in HCC treatment.

MOLECULAR THERAPY-NUCLEIC ACIDS (2021)

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Article Immunology

Inducible T-Cell Costimulator Mediates Lymphocyte/Macrophage Interactions During Liver Repair

Naresh Naik Ramavath et al.

Summary: The study investigated the role of ICOS/ICOSL signaling in liver repair, finding that CD8(+) T-lymphocytes play a key role in supporting the survival of reparative MoMFs during liver healing.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Gastroenterology & Hepatology

Group-2 Innate Lymphoid Cells Promote HCC Progression Through CXCL2-Neutrophil-Induced Immunosuppression

Xingyuan Xu et al.

Summary: The study revealed that ILC2s were highly enriched in human HCC and significantly correlated with tumor recurrence, progression-free survival, and overall survival in patients. The HCC-associated ILC2s were identified as an immune regulatory cell type that promotes tumor development, suggesting potential new treatments for HCC by targeting these cells.

HEPATOLOGY (2021)

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Article Immunology

Phase I studies of peptide vaccine cocktails derived from GPC3, WDRPUH and NEIL3 for advanced hepatocellular carcinoma

Masafumi Ikeda et al.

Summary: The two peptide cocktail vaccines showed good tolerability and potential usefulness against HCC, with stable disease reported in 52.9% and 35.7% of patients in the two studies, respectively. No dose-limiting toxicities were observed.

IMMUNOTHERAPY (2021)

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Article Oncology

Activated but impaired IFN-γ production of mucosal-associated invariant T cells in patients with hepatocellular carcinoma

Wenyong Huang et al.

Summary: The study found that MAIT cells in patients with HCC had lower levels in both peripheral blood and liver compared to healthy controls, with reduced IFN-γ production. While peripheral MAIT cells showed upregulation of HLA-DR and PD-1, intrasinusoidal MAIT cells did not exhibit significant differences. Additionally, MAIT cells were significantly enriched in the livers of HCC patients, showing high levels of activation and exhaustion markers.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Article Oncology

Off-the-shelf Vδ1 gamma delta T cells engineered with glypican-3 (GPC-3)-specific chimeric antigen receptor (CAR) and soluble IL-15 display robust antitumor efficacy against hepatocellular carcinoma

Amani Makkouk et al.

Summary: The use of engineered V delta 1 CAR T cells targeting GPC-3 in HCC shows promising efficacy and can overcome challenges faced by traditional T cell therapies in solid tumors.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Review Oncology

The Current Landscape of NKT Cell Immunotherapy and the Hills Ahead

Adam Nelson et al.

Summary: NKT cells are a specialized subset of lipid-reactive T lymphocytes that play direct and indirect roles in immunosurveillance and anti-tumor immunity. Preclinical studies have shown that NKT cell activation via delivery of exogenous glycolipids elicits a significant anti-tumor immune response. This review also examines challenges and future directions for improving the therapy.

CANCERS (2021)

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Review Oncology

Therapeutic Values of Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma: Facts and Hopes

Yijun Wang et al.

Summary: Myeloid-derived suppressor cells (MDSCs) hinder T cell infiltration into tumor sites, restricting the effectiveness of immune checkpoint inhibitors for certain patients, while targeting MDSCs has shown potent inhibitory effects in multiple tumors, including hepatocellular carcinoma. Clinically, the frequency of MDSCs is closely linked to the prognosis and predictive biomarkers of HCC patients, as well as the effectiveness of immune checkpoint inhibitors and tyrosine kinase inhibitors.

CANCERS (2021)

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Article Oncology

Cost-Effectiveness of Adjuvant Immunotherapy With Cytokine-Induced Killer Cell for Hepatocellular Carcinoma Based on a Randomized Controlled Trial and Real-World Data

Jeong-Yeon Cho et al.

Summary: Research has shown that adjuvant CIK cell immunotherapy is more cost-effective than no adjuvant therapy for patients with hepatocellular carcinoma (HCC) who have undergone potentially curative treatment, attributed to prolonged survival, reduced HCC recurrence, and improved prognosis of recurrence.

FRONTIERS IN ONCOLOGY (2021)

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Article Biochemistry & Molecular Biology

IL-10 derived from Hepatocarcinoma cells improves human induced regulatory T cells function via JAK1/STAT5 pathway in tumor microenvironment

Zhang Shaopeng et al.

Summary: The study found that treatment with hepatocarcinoma cell (HCC) supernatants increased the stability of Foxp3 and reduced apoptosis levels in human iTregs without affecting their differentiation trend. Furthermore, IL-10 levels were significantly higher in HCC supernatants compared to other groups, and blocking the IL-10 receptor neutralized the effect of HCC supernatants on iTregs. HCC supernatants also reversed the decline in Foxp3 triggered by IL-1 beta/6, potentially due to the higher expression of JAK1 and elevated phosphorylation levels of STAT5 induced by IL-10.

MOLECULAR IMMUNOLOGY (2021)

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Review Gastroenterology & Hepatology

Advances in immunotherapy for hepatocellular carcinoma

Bruno Sangro et al.

Summary: Immunotherapeutic interventions have shown effectiveness in the treatment of hepatocellular carcinoma. Checkpoint inhibitors have demonstrated strong anti-tumor activity, but other immune strategies have not yet shown consistent clinical activity. Advancing treatment to earlier stages, discovering predictive biomarkers, and exploring effective combinatorial approaches are key challenges in HCC immunotherapy.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2021)

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Review Immunology

Understanding mast cell heterogeneity at single cell resolution

Gokhan Cildir et al.

Summary: Mast cells are tissue-resident immune cells with diverse roles in various health conditions, and recent advancements in single-cell technologies have allowed for a better understanding of their development and functional characteristics. These new insights may pave the way for future research directions and therapeutic opportunities in targeting mast cell heterogeneity.

TRENDS IN IMMUNOLOGY (2021)

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Article Cell Biology

Monocytic MDSC mobilization promotes tumor recurrence after liver transplantation via CXCL10/TLR4/MMP14 signaling

Hui Liu et al.

Summary: Tumor recurrence is a major obstacle for liver transplantation in HCC patients, with inflammatory cascades promoting recurrence. The mobilization of MDSC induced by liver graft injury plays a role in promoting HCC recurrence. Targeting MDSC mobilization via CXCL10/TLR4/MMP14 signaling may represent a potential therapeutic approach to decrease post-transplant liver tumor recurrence.

CELL DEATH & DISEASE (2021)

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Article Biotechnology & Applied Microbiology

The Relationship between Hepatic Myeloid-Derived Suppressor Cells and Clinicopathological Parameters in Patients with Chronic Liver Disease

Zhijia Zhou et al.

Summary: MDSCs play a significant role in chronic liver disease and their expression is closely related to clinical characteristics, serving as a potential indicator for disease activity and liver fibrosis progression.

BIOMED RESEARCH INTERNATIONAL (2021)

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Article Immunology

A subset of Kupffer cells regulates metabolism through the expression of CD36

Camille Bleriot et al.

Summary: The study shows that tissue macrophages in the murine liver (KCs) have more subpopulations, with one of them being associated with metabolic functions. Depletion of this subpopulation leads to increased liver oxidative stress, especially in obesity.

IMMUNITY (2021)

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Article Biochemistry & Molecular Biology

MIR29A Impedes Metastatic Behaviors in Hepatocellular Carcinoma via Targeting LOX, LOXL2, and VEGFA

Ya-Ling Yang et al.

Summary: This study demonstrates the inhibitory effect of MIR29A on LOX, LOXL2, and VEGFA by targeting their 3' UTRs, leading to promotion of apoptosis and reduction in cell viability and wound healing. The results confirm that MIR29A-3p mimic can directly bind to the 3' UTRs of LOX and VEGFA to downregulate their gene and protein expression levels.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Oncology

Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study

Robin Kate Kelley et al.

Summary: This study evaluated the treatment regimens for patients with hepatocellular carcinoma and found that all regimens were tolerable and clinically active, with the T300 + D regimen showing the most favorable benefit-risk profile. Early expansion of CD8+ lymphocytes was associated with treatment response across arms.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Review Gastroenterology & Hepatology

Cancer stem cells in hepatocellular carcinoma - from origin to clinical implications

Terence Kin-Wah Lee et al.

Summary: Hepatocellular carcinoma (HCC) is an aggressive disease with poor prognosis, powered by a subset of cancer stem cells (CSCs). Research on liver CSCs has revealed their heterogeneity and unique immunobiology, suggesting potential for new research directions and therapies for HCC.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2021)

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Article Multidisciplinary Sciences

Conventional NK cells and tissue-resident ILC1s join forces to control liver metastasis

Laura Ducimetiere et al.

Summary: This study found that innate lymphocyte subpopulations cNKs and trILC1s play nonredundant roles in controlling liver metastasis seeding and outgrowth, respectively, and may contribute to developing therapies involving hepatic innate cells.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Multidisciplinary Sciences

Single-cell RNA sequencing shows the immunosuppressive landscape and tumor heterogeneity of HBV-associated hepatocellular carcinoma

Daniel Wai-Hung Ho et al.

Summary: The interaction between tumor cells and immune cells in the tumor microenvironment plays a crucial role in tumor immunity, as evidenced by single-cell RNA sequencing analysis in HBV-associated human hepatocellular carcinoma patients. This study reveals the immunosuppressive landscape and intercellular interactions, providing mechanistic insights for the development of effective immune-oncology treatments in hepatocellular carcinoma.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

Dissecting spatial heterogeneity and the immune-evasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma

Yun-Fan Sun et al.

Summary: This study used single-cell RNA sequencing to analyze circulating tumor cells from liver cancer patients, revealing that the transcriptional dynamics of CTCs are associated with stress response, cell cycle, and immune evasion signaling. Additionally, it was identified that CCL5 plays a crucial role in immune evasion of CTCs.

NATURE COMMUNICATIONS (2021)

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Article Oncology

Recombinant adenovirus expressing the fusion protein PD1PVR improves CD8+ T cell-mediated antitumor efficacy with long-term tumor-specific immune surveillance in hepatocellular carcinoma

Hailin Zhang et al.

Summary: The newly designed recombinant Ad5sPD1PVR virus significantly enhances CD8(+) T cell-mediated antitumor efficacy with long-term tumor-specific immune surveillance in hepatocellular carcinoma, and fludarabine is a promising therapeutic partner for Ad5sPD1PVR.

CELLULAR ONCOLOGY (2021)

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Article Oncology

Activating Mucosal-Associated Invariant T Cells Induces a Broad Antitumor Response

Benjamin Ruf et al.

Summary: MAIT cells exhibit potent antitumor function in vivo when activated by a combination of a synthetic riboflavin synthesis pathway-derived antigen and a TLR9 agonist. This activation leads to a strong systemic expansion and activation of MAIT cells, inducing a broad antitumor immune response in murine models. These findings suggest that MAIT cells are a promising target for cancer immunotherapy.

CANCER IMMUNOLOGY RESEARCH (2021)

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Article Oncology

Alpha-Fetoprotein- and CD40Ligand-Expressing Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma

Annabelle Vogt et al.

Summary: The combined strategy of subcutaneous vaccination with DCs transduced with AFP-coding adenoviruses and intratumoral treatment with DCs transduced with CD40L-coding adenoviruses showed promising results in inducing antitumoral immune response and leading to complete remissions and long-term survival in mice with HCC. This approach caused rapid and profound changes in the tumor environment, enhancing Th1-cytokine expression, tumor infiltration of cytotoxic T lymphocytes and DC, and tumor apoptosis, ultimately resulting in effective tumor regression of HCC.

CANCERS (2021)

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Review Oncology

Current Perspectives on B Lymphocytes in the Immunobiology of Hepatocellular Carcinoma

Miaomiao Qin et al.

Summary: This study presents the latest research on the effect of B lymphocytes infiltrating tumors in relation to hepatocellular carcinoma (HCC), analyzing their importance in prognosis and their function in the tumor microenvironment, as well as how B cell biology can be utilized to develop a therapy strategy for HCC.

FRONTIERS IN ONCOLOGY (2021)

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Article Oncology

TGF-β1 Induces Immune Escape by Enhancing PD-1 and CTLA-4 Expression on T Lymphocytes in Hepatocellular Carcinoma

Shixiang Bao et al.

Summary: Primary liver cancer is one of the most common types of cancer worldwide, with hepatocellular carcinoma accounting for the majority of cases. Immunotherapy targeting the HCC microenvironment has shown effectiveness in treatment, with studies indicating that TGF-beta 1 can regulate the expression of PD-1 and CTLA-4 on T lymphocytes, impacting their cytotoxicity towards HCC cells.

FRONTIERS IN ONCOLOGY (2021)

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Article Pharmacology & Pharmacy

Polymer Coated Oncolytic Adenovirus to Selectively Target Hepatocellular Carcinoma Cells

Mariangela Garofalo et al.

Summary: This study explored the use of polymer-coated oncolytic viruses for the treatment of hepatocellular carcinoma, showing higher therapeutic efficacy in cells expressing high levels of ASGPR. The polymer coating altered the viral properties, enhancing infectivity and immunogenic cell death compared to naked viruses.

PHARMACEUTICS (2021)

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Article Gastroenterology & Hepatology

Morphometric Analysis of Mast Cells in Tumor Predicts Recurrence of Hepatocellular Carcinoma After Liver Transplantation

Nataliya Rohr-Udilova et al.

Summary: Tumor-infiltrating immune cells, specifically mast cells, play a crucial role in the prognosis of hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation. Digital morphometric analysis of mast cells in HCC tissues can provide valuable insights into the risk of tumor recurrence, with lower intratumoral mast cell density associated with higher recurrence rates. Hepatic mast cells may be involved in antitumor immunity in HCC, and their analysis can refine the prognosis of recurrence after liver transplantation.

HEPATOLOGY COMMUNICATIONS (2021)

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Article Oncology

Neoadjuvant cabozantinib and nivolumab convert locally advanced hepatocellular carcinoma into resectable disease with enhanced antitumor immunity

Won Jin Ho et al.

Summary: A study evaluating neoadjuvant cabozantinib and nivolumab in patients with hepatocellular carcinoma (HCC) showed that 80% of patients successfully underwent hepatic resection surgery, with 42% having major pathological responses. An in-depth biospecimen profiling indicated an orchestrated contribution of B cells to antitumor immunity in HCC, with effector T cells, tertiary lymphoid structures, CD138(+) plasma cells, and a distinct spatial arrangement of B cells being enriched in responders compared to nonresponders.

NATURE CANCER (2021)

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Article Biochemistry & Molecular Biology

HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation

Qing Li et al.

Summary: YTHDF1 plays a key role in hepatocellular carcinoma, with its expression level correlated to hypoxia-induced autophagy, tumor growth, and metastasis, serving as an independent prognostic factor. HIF-1 alpha regulates YTHDF1 transcription under hypoxia to promote translation of autophagy-related genes, contributing to autophagy and malignancy in HCC progression.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Article Oncology

XCL1/Glypican-3 Fusion Gene Immunization Generates Potent Antitumor Cellular Immunity and Enhances Anti-PD-1 Efficacy

Kun Chen et al.

CANCER IMMUNOLOGY RESEARCH (2020)

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Review Oncology

Immune cells within the tumor microenvironment: Biological functions and roles in cancer immunotherapy

Xu Lei et al.

CANCER LETTERS (2020)

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Article Immunology

Type 1 Innate Lymphoid Cells Protect Mice from Acute Liver Injury via Interferon-γ Secretion for Upregulating Bcl-xL Expression in Hepatocytes

Tsukasa Nabekura et al.

IMMUNITY (2020)

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Article Oncology

Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial

Richard S. Finn et al.

JOURNAL OF CLINICAL ONCOLOGY (2020)

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Article Oncology

Increased neutrophil extracellular traps promote metastasis potential of hepatocellular carcinoma via provoking tumorous inflammatory response

Lu-Yu Yang et al.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2020)

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Review Gastroenterology & Hepatology

Epidemiology and surveillance for hepatocellular carcinoma: New trends

Amit G. Singal et al.

JOURNAL OF HEPATOLOGY (2020)

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Article Biotechnology & Applied Microbiology

Activated Hepatic Stellate Cells (HSCs) Exert Immunosuppressive Effects in Hepatocellular Carcinoma by Producing Complement C3

Yaping Xu et al.

ONCOTARGETS AND THERAPY (2020)

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Article Multidisciplinary Sciences

TGF-β induces ST2 and programs ILC2 development

Li Wang et al.

NATURE COMMUNICATIONS (2020)

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Article Oncology

Energy metabolism and cell motility defect in NK-cells from patients with hepatocellular carcinoma

Alessandra Zecca et al.

CANCER IMMUNOLOGY IMMUNOTHERAPY (2020)

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Article Oncology

Peptide vaccine as an adjuvant therapy for glypican-3-positive hepatocellular carcinoma induces peptide-specific CTLs and improves long prognosis

Masatake Taniguchi et al.

CANCER SCIENCE (2020)

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Article Oncology

MTL-CEBPA, a Small Activating RNA Therapeutic Upregulating C/EBP-a, in Patients with Advanced Liver Cancer: A First-in-Human, Multicenter, Open-Label, Phase I Trial

Debashis Sarker et al.

CLINICAL CANCER RESEARCH (2020)

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Article Oncology

Chimeric Antigen Receptor-Glypican-3 T-Cell Therapy for Advanced Hepatocellular Carcinoma: Results of Phase I Trials

Donghua Shi et al.

CLINICAL CANCER RESEARCH (2020)

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Article Oncology

Glypican-3-Specific CAR T Cells Coexpressing IL15 and IL21 Have Superior Expansion and Antitumor Activity against Hepatocellular Carcinoma

Sai Arun Batra et al.

CANCER IMMUNOLOGY RESEARCH (2020)

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Review Immunology

Helper Innate Lymphoid Cells in Human Tumors: A Double-Edged Sword?

Nicola Tumino et al.

FRONTIERS IN IMMUNOLOGY (2020)

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Article Gastroenterology & Hepatology

Glycolytic activation of monocytes regulates the accumulation and function of neutrophils in human hepatocellular carcinoma

Zhi-Peng Peng et al.

JOURNAL OF HEPATOLOGY (2020)

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Article Biotechnology & Applied Microbiology

Increased Expression of Myeloid-Derived Suppressor Cells in Patients with HBV-Related Hepatocellular Carcinoma

Tianyu Li et al.

BIOMED RESEARCH INTERNATIONAL (2020)

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Article Chemistry, Multidisciplinary

Trajectory and Functional Analysis of PD-1high CD4+CD8+ T Cells in Hepatocellular Carcinoma by Single-Cell Cytometry and Transcriptome Sequencing

Bo Zheng et al.

ADVANCED SCIENCE (2020)

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Article Oncology

EpCAM-high liver cancer stem cells resist natural killer cell-mediated cytotoxicity by upregulating CEACAM1

Dong Jun Park et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2020)

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Article Oncology

Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma

Richard S. Finn et al.

JOURNAL OF CLINICAL ONCOLOGY (2020)

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Article Medicine, Research & Experimental

32A9, a novel human antibody for designing an immunotoxin and CAR-T cells against glypican-3 in hepatocellular carcinoma

Xiaoyu Liu et al.

JOURNAL OF TRANSLATIONAL MEDICINE (2020)

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Article Biochemistry & Molecular Biology

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MOLECULAR CANCER (2020)

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The spleen contributes to the increase in PMN-MDSCs in orthotopic H22 hepatoma mice

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MOLECULAR IMMUNOLOGY (2020)

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Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib The CheckMate 040 Randomized Clinical Trial

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Cold-Inducible RNA Binding Protein as a Vaccination Platform to Enhance Immunotherapeutic Responses against Hepatocellular Carcinoma

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Adjuvant cytokine-induced killer cells with minimally invasive therapies augmented therapeutic efficacy of unresectable hepatocellular carcinoma

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JOURNAL OF CANCER RESEARCH AND THERAPEUTICS (2020)

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Efficacy and biomarker analysis of CD133-directed CAR T cells in advanced hepatocellular carcinoma: a single-arm, open-label, phase II trial

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Single-Cell RNA-Seq Analysis Reveals Microenvironmental Infiltration of Plasma Cells and Hepatocytic Prognostic Markers in HCC With Cirrhosis

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Combination therapy with dendritic cell vaccine and programmed death ligand 1 immune checkpoint inhibitor for hepatocellular carcinoma in an orthotopic mouse model

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Sustained efficacy of adjuvant immunotherapy with cytokine-induced killer cells for hepatocellular carcinoma: an extended 5-year follow-up

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CANCER IMMUNOLOGY IMMUNOTHERAPY (2019)

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Activated and Exhausted MAIT Cells Foster Disease Progression and Indicate PoorOutcomein Hepatocellular Carcinoma

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CXCR6 Inhibits Hepatocarcinogenesis by Promoting Natural Killer T- and CD4+ T-Cell-Dependent Control of Senescence

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Plasma Cell Polarization to the Immunoglobulin G Phenotype in Hepatocellular Carcinomas Involves Epigenetic Alterations and Promotes Hepatoma Progression in Mice

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Myeloid-derived suppressor cells in the patients with liver resection for hepatitis B virus-related hepatocellular carcinoma

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Landscape of infiltrating B cells and their clinical significance in human hepatocellular carcinoma

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A Positive Feedback Loop Between Cancer Stem-Like Cells and Tumor-Associated Neutrophils Controls Hepatocellular Carcinoma Progression

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Tumor-Derived α-Fetoprotein Suppresses Fatty Acid Metabolism and Oxidative Phosphorylation in Dendritic Cells

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An imbalance between stellate cells and γδT cells contributes to hepatocellular carcinoma aggressiveness and recurrence

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A human liver cell atlas reveals heterogeneity and epithelial progenitors

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JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2019)

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Activated hepatic stellate cells regulate MDSC migration through the SDF-1/CXCR4 axis in an orthotopic mouse model of hepatocellular carcinoma

Yaping Xu et al.

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Hepatic Stellate Cells Enhance Liver Cancer Progression by Inducing Myeloid-Derived Suppressor Cells through Interleukin-6 Signaling

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Combined Stereotactic Body Radiotherapy and Checkpoint Inhibition in Unresectable Hepatocellular Carcinoma: A Potential Synergistic Treatment Strategy

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FRONTIERS IN ONCOLOGY (2019)

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Goals and targets for personalized therapy for HCC

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HEPATOLOGY INTERNATIONAL (2019)

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Targeting the crosstalk between cytokine-induced killer cells and myeloid-derived suppressor cells in hepatocellular carcinoma

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Alarmin augments the antitumor immunity of lentiviral vaccine in ectopic, orthotopic and autochthonous hepatocellular carcinoma mice

Zhili Liu et al.

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High numbers of myeloid derived suppressor cells in peripheral blood and ascitic fluid of cirrhotic and HCC patients

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Endoplasmic reticulum stress induced LOX-1+CD15+ polymorphonuclear myeloid-derived suppressor cells in hepatocellular carcinoma

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IMMUNOLOGY (2018)

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Immune Responses in the Liver

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ANNUAL REVIEW OF IMMUNOLOGY, VOL 36 (2018)

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NKp46 Calibrates Tumoricidal Potential of Type 1 Innate Lymphocytes by Regulating TRAIL Expression

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Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial

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LANCET ONCOLOGY (2018)

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High number of PD-1 positive intratumoural lymphocytes predicts survival benefit of cytokine-induced killer cells for hepatocellular carcinoma patients

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Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells

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SCIENCE (2018)

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Combination therapy of hepatocellular carcinoma by DNA shuffling-based VEGF vaccine and doxorubicin

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IMMUNOTHERAPY (2018)

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Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations

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Tumor-derived exosomal HMGB1 fosters hepatocellular carcinoma immune evasion by promoting TIM-1(+) regulatory B cell expansion

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Hepatic carcinoma-associated fibroblasts enhance immune suppression by facilitating the generation of myeloid-derived suppressor cells

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Hepatic IFIT3 Predicts Interferon-α Therapeutic Response in Patients of Hepatocellular Carcinoma

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Circulating CD14+HLA-DR-/low myeloid-derived suppressor cells predicted early recurrence of hepatocellular carcinoma after surgery

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Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma

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Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial

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HCV-E2 inhibits hepatocellular carcinoma metastasis by stimulating mast cells to secrete exosomal shuttle microRNAs

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Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma

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Adjuvant immunotherapy with autologous dendritic cells for hepatocellular carcinoma, randomized phase II study

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Autophagy-deficient Kupffer cells promote tumorigenesis by enhancing mtROS-NF-κB-IL1α/β-dependent inflammation and fibrosis during the preneoplastic stage of hepatocarcinogenesis

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Tumor-Associated Neutrophils and Macrophages Promote Gender Disparity in Hepatocellular Carcinoma in Zebrafish

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Sympathetic nervous system promotes hepatocarcinogenesis by modulating inflammation through activation of alpha1-adrenergic receptors of Kupffer cells

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Dendritic Cell Immunotherapy Combined with Cytokine-Induced Killer Cells Effectively Suppresses Established Hepatocellular Carcinomas in Mice

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Mast Cells Comprise the Major of Interleukin 17-Producing Cells and Predict a Poor Prognosis in Hepatocellular Carcinoma

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Impact of myeloid-derived suppressor cell on Kupffer cells from mouse livers with hepatocellular carcinoma

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Overrepresentation of IL-10-Expressing B Cells Suppresses Cytotoxic CD4+ T Cell Activity in HBV-Induced Hepatocellular Carcinoma

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Chemokine (C-X-C Motif) Receptor 3-Positive B Cells Link Interleukin-17 Inflammation to Protumorigenic Macrophage Polarization in Human Hepatocellular Carcinoma

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Bcl11b is essential for group 2 innate lymphoid cell development

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Hepatic RIG-I Predicts Survival and Interferon-α Therapeutic Response in Hepatocellular Carcinoma

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Regulatory B cells accelerate hepatocellular carcinoma progression via CD40/CD154 signaling pathway

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NKT cell networks in the regulation of tumor immunity

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FRONTIERS IN IMMUNOLOGY (2014)

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A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C

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The functional impairment of HCC-infiltrating γδ T cells, partially mediated by regulatory T cells in a TGFβ- and IL-10-dependent manner

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The activity of γδ T cells against paediatric liver tumour cells and spheroids in cell culture

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LIVER INTERNATIONAL (2013)

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Combination of Intratumoral Invariant Natural Killer T Cells and Interferon-Gamma Is Associated with Prognosis of Hepatocellular Carcinoma after Curative Resection

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Long-Term Results of a Randomized, Observation-Controlled, Phase III Trial of Adjuvant Interferon Alfa-2b in Hepatocellular Carcinoma After Curative Resection

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The Proinflammatory Myeloid Cell Receptor TREM-1 Controls Kupffer Cell Activation and Development of Hepatocellular Carcinoma

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CANCER RESEARCH (2012)

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Tim-3/galectin-9 signaling pathway mediates T-cell dysfunction and predicts poor prognosis in patients with hepatitis B virus-associated hepatocellular carcinoma

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Oncogenic β-catenin triggers an inflammatory response that determines the aggressiveness of hepatocellular carcinoma in mice

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α-Fetoprotein impairs activation of natural killer cells by inhibiting the function of dendritic cells

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Epithelial Cell Adhesion Molecule (EpCAM) Marks Hepatocytes Newly Derived from Stem/Progenitor Cells in Humans

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Systemic Delivery of a Novel Liver-Detargeted Oncolytic Adenovirus Causes Reduced Liver Toxicity but Maintains the Antitumor Response in a Breast Cancer Bone Metastasis Model

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HUMAN GENE THERAPY (2011)

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Peritumoral neutrophils link inflammatory response to disease progression by fostering angiogenesis in hepatocellular carcinoma

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Up-regulated myeloid-derived suppressor cell contributes to hepatocellular carcinoma development by impairing dendritic cell function

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SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY (2011)

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Human NKp44+IL-22+ cells and LTi-like cells constitute a stable RORC+ lineage distinct from conventional natural killer cells

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Article Multidisciplinary Sciences

Mast Cells Mobilize Myeloid-Derived Suppressor Cells and Treg Cells in Tumor Microenvironment via IL-17 Pathway in Murine Hepatocarcinoma Model

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Systematic review and meta-analysis of interferon after curative treatment of hepatocellular carcinoma in patients with viral hepatitis

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BRITISH JOURNAL OF SURGERY (2009)

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Polarization of Tumor-Associated Neutrophil Phenotype by TGF-β: N1 versus N2 TAN

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Kupffer Cell Suppression of CD8+ T Cells in Human Hepatocellular Carcinoma Is Mediated by B7-H1/Programmed Death-1 Interactions

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Combination of peritumoral mast cells and T-regulatory cells predicts prognosis of hepatocellular carcinoma

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CANCER SCIENCE (2009)

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Myeloid Derived Suppressor Cells Inhibit Natural Killer Cells in Patients with Hepatocellular Carcinoma via the NKp30 Receptor

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HEPATOLOGY (2009)

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Enrichment of Human CD4+ Vα24/Vβ11 Invariant NKT Cells in Intrahepatic Malignant Tumors

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JOURNAL OF IMMUNOLOGY (2009)

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Type I NKT cells protect (and type II NKT cells suppress) the host's innate antitumor immune response to a B-cell lymphoma

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Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1.1- NKT cell population

Jonathan M. Coquet et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

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Hepatoma cells inhibit the differentiation and maturation of dendritic cells and increase the production of regulatory T cells

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IMMUNOLOGY LETTERS (2007)

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Histamine and spontaneously released mast cell granules affect the cell growth of human hepatocellular carcinoma cells

Nadia Lamplasi et al.

EXPERIMENTAL AND MOLECULAR MEDICINE (2007)

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Review Oncology

Systemic efficacy with oncolytic virus therapeutics: Clinical proof-of-concept and future directions

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CANCER RESEARCH (2007)

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Plasmacytoid dendritic cells do not migrate in intestinal or hepatic lymph

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JOURNAL OF IMMUNOLOGY (2006)

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The liver as an immunological organ

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HEPATOLOGY (2006)

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Differential antitumor immunity mediated by NKT cell subsets in vivo

NY Crowe et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2005)

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Correlation between expression of cyclooxygenase-2 and the presence of inflammatory cells in human primary hepatocellular carcinoma: Possible role in tumor promotion and angiogenesis

Melchiorre Cervello et al.

WORLD JOURNAL OF GASTROENTEROLOGY (2005)

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Article Oncology

Suppression of hepatocellular carcinoma by transplantation of ex-vivo immune-modulated NKT lymphocytes

M Margalit et al.

INTERNATIONAL JOURNAL OF CANCER (2005)

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α-fetoprotein impairs APC function and induces their apoptosis

SH Um et al.

JOURNAL OF IMMUNOLOGY (2004)

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NKT and CD8 lymphocytes mediate suppression of hepatocellular carcinoma growth via tumor antigen-pulsed dendritic cells

O Shibolet et al.

INTERNATIONAL JOURNAL OF CANCER (2003)

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CD1d-mediated stimulation of natural killer T cells selectively activates hepatic natural killer cells to eliminate experimentally disseminated hepatoma cells in murine liver

T Miyagi et al.

INTERNATIONAL JOURNAL OF CANCER (2003)

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γδ T cells provide an early source of interferon γ in tumor immunity

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Mast cells and human hepatocellular carcinoma

F Grizzi et al.

WORLD JOURNAL OF GASTROENTEROLOGY (2003)

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Randomized controlled trial of interferon treatment for advanced hepatocellular carcinoma

JM Llovet et al.

HEPATOLOGY (2000)

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