The co-inhibitory immune checkpoint proteins B7-H1(PD-L1) and B7-H4 in high grade glioma: From bench to bedside

Article Oncology

Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial

Antonio Omuro et al.

Summary: This study showed that TMZ + RT had better efficacy than NIVO + RT in newly diagnosed GBM patients with unmethylated MGMT promoter. However, no new safety signals were detected with NIVO in this study.

NEURO-ONCOLOGY (2023)

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Review Immunology

Recent advancements in the B7/CD28 immune checkpoint families: new biology and clinical therapeutic strategies

Marc C. Pulanco et al.

Summary: The B7/CD28 families of immune checkpoints play important roles in regulating immune cells and are closely related to various diseases. Recent studies have discovered new pathways and therapeutics for cancer therapy in this field. This review covers the newly discovered KIR3DL3/TMIGD2/HHLA2 pathways, metabolic regulation by PD-1/PD-L1 and B7-H3, the glycobiology of PD-1/PD-L1, B7x, and B7-H3, as well as the interaction between PD-L1 and B7-1. The article also discusses the resistance mechanisms to current immunotherapies targeting PD-1/PD-L1 and CTLA-4 in clinical settings, and reviews new immunotherapies targeting B7-H3, B7x, PD-1/PD-L1, and CTLA-4 in ongoing clinical trials.

CELLULAR & MOLECULAR IMMUNOLOGY (2023)

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Article Immunology

Insights from a 30-year journey: function, regulation and therapeutic modulation of PD1

Kenji Chamoto et al.

Summary: This Perspective summarizes the discovery of PD1 and its importance in cancer immunotherapy. It discusses the complex regulatory systems that govern PD1 expression and the mechanisms of PD1-blocking therapies. The article also explores the mechanism of PD1 signaling and its central role in setting the T cell activation threshold, controlling T cell proliferation, differentiation, exhaustion, and metabolic status. Furthermore, it discusses the potential combination therapies based on new insights into T cell metabolism and immune cell modulation by the microbiota, as well as the mechanisms and treatments of immune-related adverse events after PD1-targeted therapy.

NATURE REVIEWS IMMUNOLOGY (2023)

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Review Biochemistry & Molecular Biology

Glioma targeted therapy: insight into future of molecular approaches

Keyang Yang et al.

Summary: Gliomas are common brain tumors originating from glial cells. Treatment and prognosis differ significantly depending on the type of glioma. Traditional targeted therapy approaches have faced challenges, while new methods such as immunotherapy and the tumor microenvironment are gaining interest. More clinical trials are needed to evaluate the feasibility of personalized targeted therapy.

MOLECULAR CANCER (2022)

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Article Oncology

Real-world application of tumor mutational burden-high (TMB-high) and microsatellite instability (MSI) confirms their utility as immunotherapy biomarkers

M. Palmeri et al.

Summary: This real-world study reinforces the use of TMB as a predictive biomarker, and suggests that clinicians should consider treating TMB-H patients with immunotherapy.

ESMO OPEN (2022)

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Article Oncology

Circulating Immune Cell and Outcome Analysis from the Phase II Study of PD-L1 Blockade with Durvalumab for Newly Diagnosed and Recurrent Glioblastoma

Lakshmi Nayak et al.

Summary: The purpose of this study was to evaluate the efficacy of PD-L1 blockade with durvalumab in glioblastoma and investigate potential biomarkers. The results showed that recurrent glioblastoma patients had lower levels of immune cell subsets compared to newly diagnosed patients, and the use of dexamethasone also reduced immune cell subsets. An early increase in CD8 +/- Ki67 +/- cells may serve as a potential biomarker for therapeutic benefit in patients undergoing checkpoint therapy. PD-L1 blockade and combination therapy with bevacizumab were found to be ineffective in treating glioblastoma.

CLINICAL CANCER RESEARCH (2022)

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Article Oncology

Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter

Michael Lim et al.

Summary: The study evaluated the addition of the immune checkpoint inhibitor nivolumab (NIVO) to radiotherapy (RT) + temozolomide (TMZ) in newly diagnosed glioblastoma patients and found that it did not improve survival in these patients.

NEURO-ONCOLOGY (2022)

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Review Genetics & Heredity

Therapeutic and prognostic insights from the analysis of cancer mutational signatures

Samuel W. Brady et al.

Summary: Somatic mutations in cancer genomes are caused by multiple mutational processes, each leaving a characteristic imprint. Decoding these imprints can provide insights into the evolutionary history of tumors. Mutational signatures can also offer therapeutic and prognostic insights, acting as biomarkers for drug response and prognosis. Additionally, therapy-induced mutational signatures have been associated with cancer progression.

TRENDS IN GENETICS (2022)

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Article Multidisciplinary Sciences

The immune checkpoint B7x expands tumor-infiltrating Tregs and promotes resistance to anti-CTLA-4 therapy

Peter John et al.

Summary: B7x, an immune checkpoint molecule, promotes the conversion of CD4+ T cells into regulatory T cells within the tumor microenvironment. It induces transcriptomic changes in regulatory T cells, altering their phenotype to an activated and suppressive state. B7x-mediated regulation reduces the efficacy of anti-CTLA-4 treatment, but combination therapy with anti-B7x and anti-CTLA-4 overcomes this resistance and shows synergistic therapeutic efficacy.

NATURE COMMUNICATIONS (2022)

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Article Oncology

Temozolomide Treatment Alters Mismatch Repair and Boosts Mutational Burden in Tumor and Blood of Colorectal Cancer Patients

Giovanni Crisafulli et al.

Summary: The use of TMZ therapy in mCRC patients can induce MMR gene defects and TMB increase, leading to disease stabilization in a subset of patients.

CANCER DISCOVERY (2022)

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Review Oncology

Emerging Biomarkers for Immunotherapy in Glioblastoma

Nadia Mensali et al.

Summary: Immunotherapy has shown significant clinical benefits in various solid malignancies, but glioblastoma presents challenges in its treatment. Glioblastoma is the most frequent and aggressive brain cancer, and the standard treatment has not changed for over fifteen years. Except for anti-PD-1 treatment for patients with microsatellite instable cancers, there are no approved immunotherapies for glioblastoma patients. Further development of immune correlates of therapy responses and improved prognosis is needed for personalized therapy and better clinical outcomes in glioblastoma.

CANCERS (2022)

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Article Clinical Neurology

CTIM-03. PEMBROLIZUMAB MONOTHERAPY FOR MICROSATELLITE INSTABILITY-HIGH (MSI-H) OR MISMATCH REPAIR DEFICIENT (DMMR) RECURRENT GLIOMAS: RESULTS FROM THE MULTICOHORT PHASE 2 KEYNOTE-158 STUDY

Capucine Baldini et al.

NEURO-ONCOLOGY (2022)

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Article Biochemistry & Molecular Biology

A B7-CD28 Family-Based Signature Demonstrates Significantly Different Prognosis and Immunological Characteristics in Diffuse Gliomas

Xiangyang Deng et al.

Summary: This study systematically analyzed the expression profiles of B7-CD28 gene family and developed a prognostic signature based on this gene family to predict survival and immune host status in diffuse gliomas. The signature showed significant prognostic value and could be used as a biomarker to distinguish pathological grade and gene mutation status. Additionally, the signature was closely related to immune response and immune cell population, indicating its potential as a predictive marker for immunotherapy and tumor microenvironment.

FRONTIERS IN MOLECULAR BIOSCIENCES (2022)

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Article Chemistry, Multidisciplinary

Biomaterials and 3D Bioprinting Strategies to Model Glioblastoma and the Blood-Brain Barrier

Min Tang et al.

Summary: 3D-bioprinted GBM and BBB models offer promising systems and biomimetic alternatives to traditional models for more reliable mechanistic studies and preclinical drug screenings, which may eventually accelerate the drug development process for GBM.

ADVANCED MATERIALS (2021)

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Article Oncology

Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial

David A. Reardon et al.

Summary: Pembrolizumab monotherapy showed durable antitumor activity in a subset of patients with recurrent glioblastoma, with an overall response rate of 8%. Treatment-related adverse events were common, but manageable. Future studies on combination regimens may further improve outcomes.

CANCER (2021)

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Article Oncology

Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma

Lakshmi Nayak et al.

Summary: The study showed that pembrolizumab alone or in combination with bevacizumab had limited efficacy in the treatment of recurrent glioblastoma, failing to improve patient survival rates. Tumor immune biomarkers were not reliable predictors of treatment outcomes, while baseline dexamethasone use and certain tumor biomarkers may impact treatment efficacy.

CLINICAL CANCER RESEARCH (2021)

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Article Clinical Neurology

BIOM-22. RELEVANCE OF TUMOR MUTATION BURDEN (TMB) IN HIGH-GRADE GLIOMAS

Hagai Ligumsky et al.

NEURO-ONCOLOGY (2021)

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Review Oncology

PD-L1 as a biomarker of response to immune-checkpoint inhibitors

Deborah Blythe Doroshow et al.

Summary: PD-L1 expression is currently the best predictor of responsiveness to immune-checkpoint inhibitors, despite challenges in clinical use such as variability in different assays and cut-off points, as well as the lack of prospective comparisons with clinical outcomes. Nevertheless, several immunohistochemical assays have been approved for clinical use, with implications for pathology services and potential impacts on clinical outcomes. Comparison of FDA-approved PD-L1 assays, understanding of the varying implications of PD-L1 expression across different tumour types, and exploration of novel approaches to optimize its clinical utility are important topics for further research and practice.

NATURE REVIEWS CLINICAL ONCOLOGY (2021)

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Article Multidisciplinary Sciences

Neoadjuvant PD-1 blockade induces T cell and cDC1 activation but fails to overcome the immunosuppressive tumor associated macrophages in recurrent glioblastoma

Alexander H. Lee et al.

Summary: The authors conducted a high-dimensional analysis of the immune landscape in glioblastoma patients following neoadjuvant PD-1 blockade, revealing an increase in T cell infiltration and a population of progenitor exhausted T cells within the tumor. The study also identified changes in dendritic cells and myeloid cells following PD-1 blockade, suggesting the need for targeting these cells in future immunotherapeutic strategies for clinical benefit.

NATURE COMMUNICATIONS (2021)

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Article Oncology

High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types

D. J. McGrail et al.

Summary: Analysis of over 10,000 patient tumors from The Cancer Genome Atlas showed that TMB-H tumors had significantly higher response rates to immune checkpoint blockade in certain cancer types, while showing no significant benefit in others. These results do not support the use of TMB-H as a biomarker for ICB treatment across all solid cancer types, indicating the need for further tumor type-specific studies.

ANNALS OF ONCOLOGY (2021)

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Article Oncology

FDA Approval Summary: Pembrolizumab for the Treatment of Tumor Mutational Burden-High Solid for Tumors

Leigh Marcus et al.

Summary: The FDA approved pembrolizumab for the treatment of TMB-H solid tumors in adults and children, based on its significant overall response rate and duration in clinical trials. This marks the first FDA approval of a cancer treatment based on TMB, and the fourth based on a biomarker rather than primary site.

CLINICAL CANCER RESEARCH (2021)

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Article Oncology

Intracerebral administration of CTLA-4 and PD-1 immune checkpoint blocking monoclonal antibodies in patients with recurrent glioblastoma: a phase I clinical trial

Johnny Duerinck et al.

Summary: In this phase I clinical trial, intracerebral administration of NIVO and IPI following maximal safe resection of recurrent glioblastoma was found to be feasible, safe, and associated with encouraging overall survival outcomes when compared to historical cohorts. No significant difference was found in terms of progression-free survival.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Review Oncology

From Immunogenic Cell Death to Immunogenic Modulation: Select Chemotherapy Regimens Induce a Spectrum of Immune-Enhancing Activities in the Tumor Microenvironment

Kellsye P. Fabian et al.

Summary: Cancer treatment has entered the era of immunotherapy with the importance of rational combination strategies becoming clear. Chemotherapy can induce immunogenic cell stress, promoting immune response. Treatment strategies should be designed to take advantage of these effects.

FRONTIERS IN ONCOLOGY (2021)

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Review Immunology

Soluble B7-CD28 Family Inhibitory Immune Checkpoint Proteins and Anti-Cancer Immunotherapy

Muhammad Khan et al.

Summary: Soluble checkpoint molecules play important roles in immune regulation and anti-cancer immunotherapy, with correlations to tumor progression, metastasis, and prognosis. Understanding their production mechanisms and biological activities may pave the way for their use as therapeutic targets.

FRONTIERS IN IMMUNOLOGY (2021)

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Review Oncology

Targeting Tumor Microenvironment by Small-Molecule Inhibitors

Shangwei Zhong et al.

TRANSLATIONAL ONCOLOGY (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 Oncology

Enhanced B7-H4 expression in gliomas with low PD-L1 expression identifies super-cold tumors

Di Chen et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2020)

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Article Multidisciplinary Sciences

Mechanisms and therapeutic implications of hypermutation in gliomas

Mehdi Touat et al.

NATURE (2020)

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Article Oncology

Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study

Aurelien Marabelle et al.

LANCET ONCOLOGY (2020)

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Article Oncology

Pharmacologic Suppression of B7-H4 Glycosylation Restores Antitumor Immunity in Immune-Cold Breast Cancers

Xinxin Song et al.

CANCER DISCOVERY (2020)

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Article Oncology

FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors

Leigh Marcus et al.

CLINICAL CANCER RESEARCH (2019)

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Article Oncology

A T-cell-engaging B7-H4/CD3-bispecific Fab-scFv Antibody Targets Human Breast Cancer

Akira Iizuka et al.

CLINICAL CANCER RESEARCH (2019)

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Review Oncology

Challenges and potential of PD-1/PD-L1 checkpoint blockade immunotherapy for glioblastoma

Xin Wang et al.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2019)

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Article Biochemistry & Molecular Biology

Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma

Kurt A. Schalper et al.

NATURE MEDICINE (2019)

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Article Biochemistry & Molecular Biology

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma

Timothy F. Cloughesy et al.

NATURE MEDICINE (2019)

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Editorial Material Clinical Neurology

Does neoadjuvant anti-PD1 therapy improve glioblastoma outcome?

Anna S. Berghoff et al.

NATURE REVIEWS NEUROLOGY (2019)

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Article Oncology

Analysis of DNA Damage Response Gene Alterations and Tumor Mutational Burden Across 17,486 Tubular Gastrointestinal Carcinomas: Implications for Therapy

Aparna R. Parikh et al.

ONCOLOGIST (2019)

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Article Oncology

Microsatellite-Stable Tumors with High Mutational Burden Benefit from Immunotherapy

Aaron M. Goodman et al.

CANCER IMMUNOLOGY RESEARCH (2019)

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Review Oncology

Tumor Mutational Burden and Efficacy of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Jong Yeob Kim et al.

CANCERS (2019)

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Article Oncology

Expression of PD-1 by T Cells in Malignant Glioma Patients Reflects Exhaustion and Activation

Tom B. Davidson et al.

CLINICAL CANCER RESEARCH (2019)

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Article Genetics & Heredity

Tumor mutational load predicts survival after immunotherapy across multiple cancer types

Robert M. Samstein et al.

NATURE GENETICS (2019)

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Review Dermatology

Identification of responders to immune checkpoint therapy: which biomarkers have the highest value?

M. C. Liebl et al.

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY (2019)

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Review Pharmacology & Pharmacy

The Prognostic and Therapeutic Value of PD-L1 in Gliomaa

Ruo Qiao Chen et al.

FRONTIERS IN PHARMACOLOGY (2019)

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Review Oncology

Implementing TMB measurement in clinical practice: considerations on assay requirements

Reinhard Buettner et al.

ESMO OPEN (2019)

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Article Immunology

Co-inhibitory Molecule B7 Superfamily Member 1 Expressed by Tumor-Infiltrating Myeloid Cells Induces Dysfunction of Anti-tumor CD8+ T Cells

Jing Li et al.

IMMUNITY (2018)

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Review Pharmacology & Pharmacy

DNA mismatch repair in cancer

Marina Baretti et al.

PHARMACOLOGY & THERAPEUTICS (2018)

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Article Oncology

Molecular subgroups and B7-H4 expression levels predict responses to dendritic cell vaccines in glioblastoma: an exploratory randomized phase II clinical trial

Yu Yao et al.

CANCER IMMUNOLOGY IMMUNOTHERAPY (2018)

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Review Immunology

The third group of the B7-CD28 immune checkpoint family: HHLA2, TMIGD2, B7x, and B7-H3

Murali Janakiram et al.

IMMUNOLOGICAL REVIEWS (2017)

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Article Biochemistry & Molecular Biology

MicroRNA-125b-5p modulates the inflammatory state of macrophages via targeting B7-H4

Wenli Diao et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2017)

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Article Oncology

PD-L1 expression and prognostic impact in glioblastoma

Edjah K. Nduom et al.

NEURO-ONCOLOGY (2016)

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Review Immunology

Tumor infiltrating immune cells in gliomas and meningiomas

Patricia Domingues et al.

BRAIN BEHAVIOR AND IMMUNITY (2016)

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Article Oncology

B7-H4(B7x)-Mediated Cross-talk between Glioma-Initiating Cells and Macrophages via the IL6/JAK/STAT3 Pathway Lead to Poor Prognosis in Glioma Patients

Yu Yao et al.

CLINICAL CANCER RESEARCH (2016)

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Article Oncology

Tumor Cells Surviving Exposure to Proton or Photon Radiation Share a Common Immunogenic Modulation Signature, Rendering Them More Sensitive to T Cell-Mediated Killing

Sofia R. Gameiro et al.

INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS (2016)

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Review Oncology

Mouse models in oncoimmunology

Laurence Zitvogel et al.

NATURE REVIEWS CANCER (2016)

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Article Biochemistry & Molecular Biology

Cancer cell-associated cytoplasmic B7-H4 is induced by hypoxia through hypoxia-inducible factor-1α and promotes cancer cell proliferation

You-Kyoung Jeon et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2015)

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Article Medicine, Research & Experimental

An Anti-B7-H4 Antibody Drug Conjugate for the Treatment of Breast Cancer

Steven R. Leong et al.

MOLECULAR PHARMACEUTICS (2015)

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Article Oncology

Tumour-infiltrating CD4+ and CD8+ lymphocytes as predictors of clinical outcome in glioma

S. Han et al.

BRITISH JOURNAL OF CANCER (2014)

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Article Cell Biology

Structure and Cancer Immunotherapy of the B7 Family Member B7x

Hyungjun Jeon et al.

CELL REPORTS (2014)

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Review Immunology

Immunogenic Cell Death in Cancer Therapy

Guido Kroemer et al.

ANNUAL REVIEW OF IMMUNOLOGY, VOL 31 (2013)

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Article Oncology

Chemotherapy-induced immunogenic modulation of tumor cells enhances killing by cytotoxic T lymphocytes and is distinct from immunogenic cell death

James W. Hodge et al.

INTERNATIONAL JOURNAL OF CANCER (2013)

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Article Immunology

B7-H4Ig inhibits mouse and human T-cell function and treats EAE via IL-10/Treg-dependent mechanisms

Joseph R. Podojil et al.

JOURNAL OF AUTOIMMUNITY (2013)

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Article Oncology

B7-H1 is correlated with malignancy-grade gliomas but is not expressed exclusively on tumor stem-like cells

Yu Yao et al.

NEURO-ONCOLOGY (2009)

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Article Oncology

B7-H4 is preferentially expressed in non-dividing brain tumor cells and in a subset of brain tumor stem-like cells

Yu Yao et al.

JOURNAL OF NEURO-ONCOLOGY (2008)

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Article Multidisciplinary Sciences

B7x: A widely expressed B7 family member that inhibits T cell activation

XX Zang et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2003)

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Article Immunology

B7-H4, a molecule of the B7 family, negatively regulates T cell immunity

GL Sica et al.

IMMUNITY (2003)

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Article Immunology

B7S1, a novel B7 family member that negatively regulates T cell activation

DVR Prasad et al.

IMMUNITY (2003)

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Review Immunology

The B7-CD28 superfamily

AH Sharpe et al.

NATURE REVIEWS IMMUNOLOGY (2002)

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The co-inhibitory immune checkpoint proteins B7-H1(PD-L1) and B7-H4 in high grade glioma: From bench to bedside

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