☆ 4.8 Review

Targeting tumor-associated macrophages for the immunotherapy of glioblastoma: Navigating the clinical and translational landscape

FRONTIERS IN IMMUNOLOGY (2022)

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Review Chemistry, Multidisciplinary

Chemistry of Lipid Nanoparticles for RNA Delivery Published as part of the Accounts of Chemical Research special issue mRNA Therapeutics

Gaurav Sahay et al.

Summary: This paper discusses the importance of lipid nanoparticles (LNPs) in RNA delivery. LNPs have great potential in mRNA delivery and can be used for the treatment of infectious diseases, cancer, and rare genetic diseases. The paper introduces the core features of LNPs, the theory and methods of LNP self-assembly, the components and overall attributes of LNPs, and provides an outlook on the future of RNA therapies.

ACCOUNTS OF CHEMICAL RESEARCH (2022)

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Article Chemistry, Multidisciplinary

Engineering Macrophage Exosome Disguised Biodegradable Nanoplatform for Enhanced Sonodynamic Therapy of Glioblastoma

Tingting Wu et al.

Summary: Sonodynamic therapy (SDT) is a promising cancer treatment modality for glioblastoma (GBM) due to its high tissue penetration and minimal damage to normal tissues. However, the blood-brain barrier (BBB) and hypoxic microenvironment present challenges to SDT efficiency. In this study, a biodegradable nanoplatform (CSI@Ex-A) was developed, which could effectively penetrate the BBB and target cancer cells. The nanoplatform releases hydrogen peroxide (H2O2) and oxygen (O-2) to relieve tumor hypoxia, thereby enhancing the efficacy of SDT.

ADVANCED MATERIALS (2022)

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Article Nanoscience & Nanotechnology

TfR-T12 short peptide and pH sensitive cell transmembrane peptide modified nano-composite micelles for glioma treatment via remodeling tumor microenvironment

Ping Sun et al.

Summary: Two amphiphilic block copolymers were synthesized to construct nano-composite micelles for encapsulating paclitaxel and imiquimod. The nano-composite micelles achieved targeted delivery through the blood-brain barrier and showed pH-sensitive uptake efficiency. They also significantly regulated the immunosuppression in the tumor microenvironment and exhibited good anti-tumor effects.

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE (2022)

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Article Multidisciplinary Sciences

Single-cell analysis of human glioma and immune cells identifies S100A4 as an immunotherapy target

Nourhan Abdelfattah et al.

Summary: This study identifies molecular phenotypes of immune-suppressive and -promoting myeloid cells in GBM through single cell RNA sequencing and discovers S100A4 as a regulator of immune suppressive T and myeloid cells in GBM. The study reveals extensive spatial and molecular heterogeneity in immune infiltrates and identifies nine distinct myeloid cell subtypes, with five being prognostic indicators of glioma patient survival.

NATURE COMMUNICATIONS (2022)

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Article Engineering, Biomedical

A Micro-Environment Regulator for Filling the Clinical Treatment Gap after a Glioblastoma Operation

Yiwen Zhang et al.

Summary: An immediate and mild postoperative local treatment strategy is developed using an injectable hydrogel system to regulate the postoperative microenvironment and delay recurrence of glioblastoma. This hydrogel system can block the recruitment of microglia/macrohpages and activate cytotoxic T cells, effectively inhibiting glioblastoma recurrence and gaining valuable time for subsequent chemotherapy.

ADVANCED HEALTHCARE MATERIALS (2022)

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Article Oncology

CD70 as an actionable immunotherapeutic target in recurrent glioblastoma and its microenvironment

Mathieu Seyfrid et al.

Summary: This study identifies CD70 as a potential therapeutic target for recurrent glioblastoma stem cells (CSCs). Targeting CD70 with CAR-T therapy significantly improves prognosis in animal models and the CD70/CD27 axis may provide a viable polytherapeutic avenue for targeting both glioblastoma and its tumor immune microenvironment.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

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Article Chemistry, Multidisciplinary

In situ targeting nanoparticles-hydrogel hybrid system for combined chemo-immunotherapy of glioma

Xiaoqi Wang et al.

Summary: Glioma is a highly malignant brain tumor, and traditional chemotherapy has limitations. In this study, a novel hydrogel delivery system was developed for enhanced chemo-immunotherapy of glioma through local delivery of chemotherapy drugs and immunoadjuvants.

JOURNAL OF CONTROLLED RELEASE (2022)

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Article Oncology

Characterization of systemic immunosuppression by IDH mutant glioma small extracellular vesicles

Nils Ludwig et al.

Summary: This study reveals the role of tumor-derived glioma small extracellular vesicles (TEX) in immunomodulation in IDH mutant gliomas. The findings demonstrate that mutIDH TEX are more immunosuppressive compared to wtIDH TEX. Injection of mutIDH TEX reduces tumor-infiltrating immune cells and increases circulating monocytes, even accelerating tumor growth and mortality.

NEURO-ONCOLOGY (2022)

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Article Immunology

Single-cell RNA sequencing reveals evolution of immune landscape during glioblastoma progression

Alan T. Yeo et al.

Summary: Using single-cell transcriptomics and flow cytometry, this study investigated the changes in immune cell composition during the progression of glioblastoma (GBM). The results revealed a transition from pro-inflammatory microglia to infiltrating macrophages and suppressor cells as the tumor advanced.

NATURE IMMUNOLOGY (2022)

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Article Oncology

USF1/CD90 signaling in maintaining glioblastoma stem cells and tumor-associated macrophages adhesion

Yuanshuai Zhou et al.

Summary: This study reveals that the USF1/CD90 axis plays a crucial role in promoting malignant growth and stemness of glioblastoma stem cells (GSCs) through physical interaction with tumor-associated macrophages (TAMs). The findings suggest that targeting the USF1/CD90 axis may provide a potential therapeutic strategy for glioblastoma treatment.

NEURO-ONCOLOGY (2022)

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Article Multidisciplinary Sciences

Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion

Nian Jiang et al.

Summary: This study reveals that the co-enhancement of mitochondrial fatty acid oxidation (FAO) enzymes and immune checkpoint CD47 is dominant in recurrent GBM patients with poor prognosis. Inhibition of FAO can impair tumor growth and reduce CD47 anti-phagocytosis, and combining FAO inhibition and anti-CD47 antibody can enhance radiation control of regrown tumors and boost macrophage phagocytosis.

NATURE COMMUNICATIONS (2022)

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Article Biotechnology & Applied Microbiology

Therapeutic nucleus-access BNCT drug combined CD47-targeting gene editing in glioblastoma

Jiejian Chen et al.

Summary: The study achieves nuclear targeting of boron by utilizing the nuclear translocation property of doxorubicin, constructing a new nanoliposome delivery system that combines boron neutron capture therapy (BNCT) with immunotherapy, significantly improving the survival rate of tumor-bearing mice.

JOURNAL OF NANOBIOTECHNOLOGY (2022)

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Article Medicine, Research & Experimental

Glioma-targeted delivery of exosome-encapsulated antisense oligonucleotides using neural stem cells

Tomasz Adamus et al.

Summary: Neural stem cells (NSCs) can effectively transport antisense oligonucleotides (ASOs) targeting STAT3 protein to glioma microenvironment. NSC-derived exosomes loaded with CpG-STAT3ASO stimulate immune activity and inhibit tumor growth.

MOLECULAR THERAPY-NUCLEIC ACIDS (2022)

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Article Biochemistry & Molecular Biology

Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial

Lacey J. Padron et al.

Summary: Chemotherapy combined with immunotherapy has improved the treatment of certain solid tumors, however, finding effective regimens for pancreatic ductal adenocarcinoma (PDAC) remains a challenge. A randomized phase 2 trial evaluated the efficacy of nivolumab and sotigalimab with chemotherapy in metastatic PDAC patients. The primary endpoint of 1-year overall survival was met for nivo/chemo but not for sotiga/chemo or sotiga/nivo/chemo. Biomarker analyses identified immune signatures associated with survival for different treatment groups.

NATURE MEDICINE (2022)

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Article Cell Biology

Intracavity generation of glioma stem cell-specific CAR macrophages primes locoregional immunity for postoperative glioblastoma therapy

Chen Chen et al.

Summary: Researchers have developed a cavity-injectable nanoporter-hydrogel superstructure to prevent relapse of glioblastoma multiforme (GBM). This superstructure introduces glioma stem cell-specific chimeric antigen receptor (CAR) genes into macrophages/microglia, stimulating an antitumor immune response and preventing postoperative relapse.

SCIENCE TRANSLATIONAL MEDICINE (2022)

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Article Medicine, Research & Experimental

Arginine deprivation alters microglial polarity and synergizes with radiation to eradicate non-arginine-auxotrophic glioblastoma tumors

Nabil Hajji et al.

Summary: The study suggests that ADI-PEG20, an arginine-depleting agent, can potentiate the efficacy of radiotherapy in glioblastoma, leading to improved treatment outcomes without significant toxicity. Furthermore, ADI-PEG20 also promotes an anti-tumor immune response. This study provides a promising strategy for GBM treatment that should be further evaluated in clinical trials.

JOURNAL OF CLINICAL INVESTIGATION (2022)

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Article Biochemistry & Molecular Biology

Exploration and functionalization of M1-macrophage extracellular vesicles for effective accumulation in glioblastoma and strong synergistic therapeutic effects

Xiaojun Wang et al.

Summary: The researchers successfully developed M1-like macrophage-derived extracellular vesicles (M1EVs) for the treatment of glioblastoma multiforme (GBM). These M1EVs achieved synergistic immunomodulation, chemiexcited photodynamic therapy (CDT), and hypoxia-activated chemotherapy in GBM, leading to a potent therapeutic effect. The results demonstrated the excellent efficacy of CCA-M1EVs against GBM in cell-derived and patient-derived xenograft models.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2022)

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Article Oncology

1p/19q co-deletion status is associated with distinct tumor-associated macrophage infiltration in IDH mutated lower-grade gliomas

Yanyu Zhang et al.

Summary: This study found that in IDH-mutated LGGs, most TAMs expressed M1 activation markers CD86 and TNF, with some TAMs co-expressing both M1 and M2-related markers. Higher levels of TAMs expressing M2-related markers were observed in 1p/19q non-codeletion IDH-mutated LGGs compared to 1p/19q codeletion LGGs. Inhibition of M-CSF and TGF beta 1 signaling decreased tumor growth and modulated TAM phenotype in a glioma mouse model, indicating a potential role of these proteins in regulating TAM phenotype in glioma.

CELLULAR ONCOLOGY (2021)

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Article Nanoscience & Nanotechnology

Reeducating Tumor-Associated Macrophages Using CpG@Au Nanocomposites to Modulate Immunosuppressive Microenvironment for Improved Radio-Immunotherapy

Yuhua Cao et al.

Summary: The study demonstrated the use of CpG-decorated gold nanoparticles to improve the efficacy of radiotherapy and immune checkpoint blockade therapy. By re-educating immunosuppressive M2 tumor-associated macrophages to immunostimulatory M1 counterparts, the treatment effectively modulated the tumor-immune microenvironment for synergistic RT/ICB, leading to consistent abscopal responses in a bilateral tumor model.

ACS APPLIED MATERIALS & INTERFACES (2021)

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Article Nanoscience & Nanotechnology

Macrophage-Mediated Porous Magnetic Nanoparticles for Multimodal Imaging and Postoperative Photothermal Therapy of Gliomas

Sheng Wang et al.

Summary: A macrophage loaded with a photothermal nanoprobe was developed to cross the blood-brain barrier and accumulate into deep gliomas for multimodal imaging and guided surgery purposes. This nanoplatform shows promise for achieving accurate diagnosis, imaging-guided surgery, and effective photothermal therapy for gliomas.

ACS APPLIED MATERIALS & INTERFACES (2021)

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Article Chemistry, Multidisciplinary

Macrophage Membrane-Camouflaged Responsive Polymer Nanogels Enable Magnetic Resonance Imaging-Guided Chemotherapy/Chemodynamic Therapy of Orthotopic Glioma

Tingting Xiao et al.

Summary: The study introduces a multifunctional polymer nanogel camouflaged with macrophage membranes for MR imaging-guided chemotherapy of glioma. The nanogel exhibits dual pH and redox-responsive release profiles, enhancing chemotherapy/CDT efficacy.

ACS NANO (2021)

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Article Oncology

Modification of Extracellular Matrix Enhances Oncolytic Adenovirus Immunotherapy in Glioblastoma

Juri Kiyokawa et al.

Summary: This study demonstrates the immune modulatory impact of ICOVIR17, which mediates HA degradation within the GBM ECM and subsequently modifies the immune landscape of the TME. It offers a mechanistic combination immunotherapy with PD-L1/PD-1 blockade that remodels innate and adaptive immune cells.

CLINICAL CANCER RESEARCH (2021)

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Review Biochemistry & Molecular Biology

Hallmarks of response, resistance, and toxicity to immune checkpoint blockade

Golnaz Morad et al.

Summary: This passage discusses the unprecedented advances in cancer treatment with immune checkpoint blockade (ICB), highlighting the critical need for insights into factors intrinsic and extrinsic to the host that impact ICB response and toxicity. There has been substantial progress in understanding the impact of host-intrinsic factors and the exposome on host physiology and response to treatment, representing the hallmarks of response, resistance, and toxicity to ICB in current day.

CELL (2021)

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Article Chemistry, Multidisciplinary

Systemic dendrimer delivery of triptolide to tumor-associated macrophages improves anti-tumor efficacy and reduces systemic toxicity in glioblastoma

Kevin Liaw et al.

Summary: In this study, a novel dendrimer-triptolide conjugate was developed to target tumor-associated macrophages in glioblastoma, showing improved phenotype switching from pro-tumor to anti-tumor expression. This targeted delivery strategy significantly reduced systemic toxicities and achieved enhanced tumor burden amelioration in an orthotopic model of glioblastoma. Dendrimers are proposed as a promising platform for effective glioblastoma treatment by improving efficacy while reducing systemic toxicities.

JOURNAL OF CONTROLLED RELEASE (2021)

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Article Chemistry, Multidisciplinary

Hydrogel loading functionalized PAMAM/shRNA complex for postsurgical glioblastoma treatment

Jie Song et al.

Summary: A gene complex-loaded thermo-sensitive hydrogel was designed to inhibit immune escape of residual glioblastoma cells after surgery, significantly prolonging the survival time of mice.

JOURNAL OF CONTROLLED RELEASE (2021)

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Review Oncology

Toll-like receptors and toll-like receptor-targeted immunotherapy against glioma

Yang Xun et al.

Summary: Glioma is a fast proliferating and highly invasive brain tumor that is difficult to treat and often recurs. Toll-like receptors play dual roles in the glioma microenvironment, eliciting both anti-tumoral and pro-tumoral responses. Targeting TLRs in glioma treatment may provide new strategies for immunotherapy.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2021)

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Article Chemistry, Multidisciplinary

A Virus-Mimicking Nucleic Acid Nanogel Reprograms Microglia and Macrophages for Glioblastoma Therapy

Xihui Gao et al.

Summary: Immunotherapy is a promising approach for treating cancers, but its effectiveness in glioblastoma treatment is limited due to the immunosuppressive tumor microenvironment. A virus-mimicking membrane-coated nucleic acid nanogel, Vir-Gel, has been developed to reprogram microglia and macrophages from a pro-invasive M2 phenotype to an anti-tumor M1 phenotype. This approach significantly enhances the targetability and cell uptake efficiency of therapeutic miRNA, demonstrating improved tumor inhibition efficacy.

ADVANCED MATERIALS (2021)

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Article Chemistry, Multidisciplinary

Multifunctional ginsenoside Rg3-based liposomes for glioma targeting therapy

Ying Zhu et al.

Summary: The study found that using a liposomal system based on ginsenoside Rg3 can effectively improve the targeting of brain tumors, enhance the delivery of drugs, and play a beneficial role in anti-tumor treatment.

JOURNAL OF CONTROLLED RELEASE (2021)

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Review Chemistry, Multidisciplinary

Immune Cell Membrane-Coated Biomimetic Nanoparticles for Targeted Cancer Therapy

Fatemeh Oroojalian et al.

Summary: Nanotechnology offers promising opportunities for cancer management, particularly through biomimetic approaches using immune cell membranes to coat nanoparticles for improved stability and targeting; the surface proteins from immune cells can provide various functionalities to nanoparticles, enhancing their efficacy and reducing toxicity.

SMALL (2021)

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Article Multidisciplinary Sciences

Single-cell RNA sequencing reveals functional heterogeneity of glioma-associated brain macrophages

Natalia Ochocka et al.

Summary: The study reveals molecular heterogeneity among myeloid cells in naive and glioma-bearing brains in mice, as well as a gender-specific gene expression in glioma-activated microglia, which is also supported by bulk and scRNA-seq data from human diffuse gliomas.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

Cell membrane coating integrity affects the internalization mechanism of biomimetic nanoparticles

Lizhi Liu et al.

Summary: Cell membrane coated nanoparticles have unique properties that make them attractive for nanomedical applications, but it has been found that most nanoparticles are only partially coated. This partial coating can impact the biological fate of the nanoparticles.

NATURE COMMUNICATIONS (2021)

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Review Oncology

Cellular and Molecular Mechanisms Underlying Glioblastoma and Zebrafish Models for the Discovery of New Treatments

Pedro Reimunde et al.

Summary: Glioblastoma (GBM) is a highly challenging brain tumor with poor prognosis and limited treatment options. Research on cellular heterogeneity and genetic alterations has led to the development of zebrafish models for studying GBM physiopathology and testing new drugs, offering hope for improved diagnosis and treatment outcomes.

CANCERS (2021)

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Article Oncology

MET overexpression contributes to STAT4-PD-L1 signaling activation associated with tumor-associated, macrophages-mediated immunosuppression in primary glioblastomas

Qiang-Wei Wang et al.

Summary: The study revealed that the activation of the MET-STAT4-PD-L1 axis and the upregulation of tumor-associated macrophages are associated with immune evasion and shorter survival time in patients with primary GBM. These findings suggest potential clinical strategies for targeted therapy combined with immunotherapy in patients with primary GBM.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Review Oncology

Oncolytic viruses encoding bispecific T cell engagers: a blueprint for emerging immunovirotherapies

Johannes P. W. Heidbuechel et al.

Summary: Bispecific T cell engagers (BiTEs) and oncolytic viruses (OVs) are emerging cancer immunotherapies that redirect T cells to tumor surface antigens and selectively infect malignant cells to mediate tumor vaccination effects, respectively. These two approaches can synergize with each other and with other immunotherapies, such as CAR T cells and immune checkpoint inhibitors, to enhance anti-tumor effects.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2021)

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Article Engineering, Biomedical

Conjugation of glucosylated polymer chains to checkpoint blockade antibodies augments their efficacy and specificity for glioblastoma

Tao Yang et al.

Summary: Monoclonal antibodies conjugated with multiple polymer chains, functionalized to target glucose transporter 1 and detaching in the reductive tumor microenvironment, can enhance the potency and safety of checkpoint blockade therapy for glioblastoma. This approach showed promising results in mouse models, reinvigorating antitumor immune responses and inducing protective immunological memory against tumor rechallenge.

NATURE BIOMEDICAL ENGINEERING (2021)

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Article Neurosciences

Single-cell profiling of myeloid cells in glioblastoma across species and disease stage reveals macrophage competition and specialization

Ana Rita Pombo Antunes et al.

Summary: By utilizing single-cell RNA sequencing and CITE-seq, this study reveals the complexity of the immune landscape in glioblastomas, including conserved populations of dendritic cells and macrophages. The results indicate that microglia-derived tumor-associated macrophages dominate in newly diagnosed tumors, but are replaced by monocyte-derived TAMs in recurrences.

NATURE NEUROSCIENCE (2021)

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Article Genetics & Heredity

Single-cell characterization of macrophages in glioblastoma reveals MARCO as a mesenchymal pro-tumor marker

Andrew X. Chen et al.

Summary: This study identified a pro-tumor subpopulation of bone marrow-derived macrophages characterized by MARCO, which is exclusively found in IDH1-wild-type glioblastomas. MARCO expression is associated with worse prognosis and mesenchymal subtype, and significantly altered during treatment with anti-PD1 checkpoint inhibitors, suggesting potential therapeutic targets for preventing their recruitment.

GENOME MEDICINE (2021)

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Article Chemistry, Multidisciplinary

A Noninvasive Gut-to-Brain Oral Drug Delivery System for Treating Brain Tumors

Yang-Bao Miao et al.

Summary: An oral prodrug delivery system has been developed to target gliomas by overcoming the intestinal epithelial barrier and the blood-brain barrier. The prodrug specifically targets intestinal M cells, crosses the barriers, and releases the active drug at the tumor site for improved therapeutic efficacy.

ADVANCED MATERIALS (2021)

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Article Oncology

Neoadjuvant Selicrelumab, an Agonist CD40 Antibody, Induces Changes in the Tumor Microenvironment in Patients with Resectable Pancreatic Cancer

Katelyn T. Byrne et al.

Summary: A neoadjuvant clinical trial with agonistic CD40 mAb in resectable pancreatic ductal adenocarcinoma patients showed that the treatment led to enrichment of T cells in the tumor microenvironment, reduced tumor fibrosis, fewer M2-like tumor-associated macrophages, and increased mature dendritic cells. Additionally, systemic inflammatory cytokines were increased after the treatment, providing insights for subsequent clinical trials targeting CD40 in cancer.

CLINICAL CANCER RESEARCH (2021)

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Article Multidisciplinary Sciences

Tissue-resident macrophages provide a pro-tumorigenic niche to early NSCLC cells

Maria Casanova-Acebes et al.

Summary: Macrophages play a crucial role in shaping the tumor microenvironment and tumor immunity, with tissue-resident macrophages identified as key contributors to early lung cancer progression. Targeting tissue-resident macrophages may offer new possibilities for prevention and treatment of early lung cancer lesions.

NATURE (2021)

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Review Nanoscience & Nanotechnology

Extracellular vesicles as a next-generation drug delivery platform

Inge Katrin Herrmann et al.

Summary: Extracellular vesicles play a crucial role in cell-to-cell communication and can serve as drug carriers with advantages over synthetic carriers. However, clinical translation of extracellular vesicle-based therapies remains challenging, requiring further research and development efforts.

NATURE NANOTECHNOLOGY (2021)

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Review Oncology

The 2021 WHO Classification of Tumors of the Central Nervous System: a summary

David N. Louis et al.

Summary: The fifth edition of the WHO Classification of Tumors of the Central Nervous System integrates molecular diagnostics into CNS tumor classification, introduces different approaches to tumor nomenclature and grading, and emphasizes the importance of integrated diagnoses and layered reports.

NEURO-ONCOLOGY (2021)

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Article Multidisciplinary Sciences

Synergistic immunotherapy of glioblastoma by dual targeting of IL-6 and CD40

Fan Yang et al.

Summary: This study demonstrates that IL-6 blockade, in combination with a CD40 agonist, overcomes macrophage-mediated immunosuppression and sensitizes glioblastoma to immune checkpoint blockade in preclinical models, providing promising opportunities for GBM and other solid tumors.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

Agonistic CD40 therapy induces tertiary lymphoid structures but impairs responses to checkpoint blockade in glioma

Luuk van Hooren et al.

Summary: This study demonstrates that the use of immunostimulatory CD40 antibodies in glioma models promotes the formation of tertiary lymphoid structures but does not improve survival and impairs the response to immune checkpoint blockade.

NATURE COMMUNICATIONS (2021)

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Article Immunology

Enriched Environment Cues Suggest a New Strategy to Counteract Glioma: Engineered rAAV2-IL-15 Microglia Modulate the Tumor Microenvironment

Alessandro Mormino et al.

Summary: Exposure to an enriched environment increases the overall survival rate of tumor-bearing mice by promoting a pro-inflammatory phenotype of microglia and enhancing the cytotoxic activity of NK cells in glioma. By delivering engineered microglia with forced IL-15 production, NK cell viability is increased, leading to suppression of tumor growth. This approach demonstrates a high potential for clinical translatability in designing a new therapy perspective for glioma patients.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Oncology

Intratumoral combination therapy with poly(I:C) and resiquimod synergistically triggers tumor-associated macrophages for effective systemic antitumoral immunity

Clement Anfray et al.

Summary: This study demonstrated the superior efficacy of poly(I:C) combined with R848 compared to single treatments or combined with R837 in reprogramming macrophages towards M1-like antitumor effectors in vitro, leading to significant prevention of tumor growth and metastasis in lung cancer and fibrosarcoma mouse models. The therapy also induced systemic antitumoral response and resistance to tumor rechallenge through boosted macrophage cytotoxic activity and T-cell proliferation. Proteomic experiments validated the activation of innate immunity by poly(I:C)+R848 combination, with the key activation of the STAT1 pathway.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Article Medicine, Research & Experimental

SLIT2/ROBO signaling in tumor-associated microglia and macrophages drives glioblastoma immunosuppression and vascular dysmorphia

Luiz H. Geraldo et al.

Summary: SLIT2 expression is associated with malignant progression and poor survival in glioblastoma patients. Knockdown of SLIT2 in glioma cells reduces tumor growth and enhances efficacy of chemotherapy and immunotherapy by improving tumor vessel function and promoting a cytotoxic gene expression profile. SLIT2 signaling through macrophage ROBO receptors may serve as a novel regulator of the GBM microenvironment and a potential immunotherapeutic target for brain tumors.

JOURNAL OF CLINICAL INVESTIGATION (2021)

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Article Medicine, Research & Experimental

Immunostimulatory bacterial antigen-armed oncolytic measles virotherapy significantly increases the potency of anti-PD1 checkpoint therapy

Eleni Panagioti et al.

Summary: This study found that combination NAP-immunovirotherapy induced massive influx of lymphoid cells in mouse brain, with CD8+ T cell predominance; therapeutic efficacy was CD8+ T cell dependent. Inhibition of the IFN response pathway using the JAK1/JAK2 inhibitor ruxolitinib decreased PD-L1 expression on myeloid-derived suppressor cells in the brain and further potentiated the therapeutic effect of MV-s-NAP-uPA and anti-PD1.

JOURNAL OF CLINICAL INVESTIGATION (2021)

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Article Chemistry, Multidisciplinary

Progress on Modulating Tumor-Associated Macrophages with Biomaterials

Meilyn Sylvestre et al.

ADVANCED MATERIALS (2020)

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Review Medicine, Research & Experimental

CD40 Agonist Antibodies in Cancer Immunotherapy

Robert H. Vonderheide

ANNUAL REVIEW OF MEDICINE, VOL 71, 2020 (2020)

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Article Cell Biology

Meningeal lymphatic vessels regulate brain tumor drainage and immunity

Xueting Hu et al.

CELL RESEARCH (2020)

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Article Multidisciplinary Sciences

VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours

Eric Song et al.

NATURE (2020)

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Article Biochemistry & Molecular Biology

Immune profiling of human tumors identifies CD73 as a combinatorial target in glioblastoma

Sangeeta Goswami et al.

NATURE MEDICINE (2020)

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Review Multidisciplinary Sciences

The biology, function, and biomedical applications of exosomes

Raghu Kalluri et al.

SCIENCE (2020)

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Article Multidisciplinary Sciences

Microglia monitor and protect neuronal function through specialized somatic purinergic junctions

Csaba Cserep et al.

SCIENCE (2020)

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Review Oncology

The CXCL12-CXCR4/CXCR7 axis as a mechanism of immune resistance in gastrointestinal malignancies

Sara K. Daniel et al.

SEMINARS IN CANCER BIOLOGY (2020)

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Article Oncology

NRG/RTOG 1122: A phase 2, double-blinded, placebo-controlled study of bevacizumab with and without trebananib in patients with recurrent glioblastoma or gliosarcoma

Eudocia Q. Lee et al.

CANCER (2020)

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Single-Cell Mapping of Human Brain Cancer Reveals Tumor-Specific Instruction of Tissue-Invading Leukocytes

Ekaterina Friebel et al.

CELL (2020)

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Interrogation of the Microenvironmental Landscape in Brain Tumors Reveals Disease-Specific Alterations of Immune Cells

Florian Klemm et al.

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Article Cell & Tissue Engineering

The Rational Development of CD133-Targeting Immunotherapies for Glioblastoma

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CELL STEM CELL (2020)

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Review Immunology

The CD47-SIRPα Immune Checkpoint

Meike E. W. Logtenberg et al.

IMMUNITY (2020)

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Article Biochemistry & Molecular Biology

O-Vanillin Attenuates the TLR2 Mediated Tumor-Promoting Phenotype of Microglia

Paul Triller et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Article Oncology

Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma The CheckMate 143 Phase 3 Randomized Clinical Trial

David A. Reardon et al.

JAMA ONCOLOGY (2020)

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Article Nanoscience & Nanotechnology

Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR-Cas gene editing

Qiang Cheng et al.

NATURE NANOTECHNOLOGY (2020)

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Article Oncology

First-in-human, dose-escalation, phase 1 study of anti-angiopoietin-2 LY3127804 as monotherapy and in combination with ramucirumab in patients with advanced solid tumours

Juan Martin-Liberal et al.

BRITISH JOURNAL OF CANCER (2020)

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Review Oncology

Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy

Christopher A. Chuckran et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2020)

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Review Oncology

Oncolytic viruses for cancer immunotherapy

Otto Hemminki et al.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2020)

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Article Biochemistry & Molecular Biology

IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression

Ahmed Sadik et al.

CELL (2020)

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