Combinatorial blockade for cancer immunotherapy: targeting emerging immune checkpoint receptors

Frontiers in Immunology

Immunology

Sachin Patnaik¹  Dia Roy¹  Cassandra Gilmour²  Li Lily Wang² 

[1] Department of Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Cleveland, OH, United States;Department of Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Cleveland, OH, United States;Department of Molecular Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, United States;

关键词: immune checkpoint inhibitors;    combinatorial immunotherapies;    PD-1;    CTLA-4;    VISTA;    TIGIT;    TIM3;    LAG3;   

DOI  :  10.3389/fimmu.2023.1264327

 received in 2023-07-20, accepted in 2023-09-26,  发布年份 2023

来源: Frontiers

【 摘 要 】

The differentiation, survival, and effector function of tumor-specific CD8+ cytotoxic T cells lie at the center of antitumor immunity. Due to the lack of proper costimulation and the abundant immunosuppressive mechanisms, tumor-specific T cells show a lack of persistence and exhausted and dysfunctional phenotypes. Multiple coinhibitory receptors, such as PD-1, CTLA-4, VISTA, TIGIT, TIM-3, and LAG-3, contribute to dysfunctional CTLs and failed antitumor immunity. These coinhibitory receptors are collectively called immune checkpoint receptors (ICRs). Immune checkpoint inhibitors (ICIs) targeting these ICRs have become the cornerstone for cancer immunotherapy as they have established new clinical paradigms for an expanding range of previously untreatable cancers. Given the nonredundant yet convergent molecular pathways mediated by various ICRs, combinatorial immunotherapies are being tested to bring synergistic benefits to patients. In this review, we summarize the mechanisms of several emerging ICRs, including VISTA, TIGIT, TIM-3, and LAG-3, and the preclinical and clinical data supporting combinatorial strategies to improve existing ICI therapies.

【 授权许可】

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Copyright © 2023 Roy, Gilmour, Patnaik and Wang