Immunological evasion is one of the defining characteristics of cancers, as the immune modification of an immune checkpoint (IC) confers immune evasion capabilities to tumor cells. Multiple ICs, such as programmed cell death protein-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), can bind to their respective receptors and reduce tumor immunity in a variety of ways, including blocking immune cell activation signals. IC blockade (ICB) therapies targeting these checkpoint molecules have demonstrated significant clinical benefits. This is because antibody-based IC inhibitors and a variety of specific small molecule inhibitors can inhibit key oncogenic signaling pathways and induce durable tumor remission in patients with a variety of cancers. Deciphering the roles and regulatory mechanisms of these IC molecules will provide crucial theoretical guidance for clinical treatment. In this review, we summarize the current knowledge on the functional and regulatory mechanisms of these IC molecules at multiple levels, including epigenetic regulation, transcriptional regulation, and post-translational modifications. In addition, we provide a summary of the medications targeting various nodes in the regulatory pathway, and highlight the potential of newly identified IC molecules, focusing on their potential implications for cancer diagnostics and immunotherapy.

Zerui GAO;Xingyi LING;Chengyu SHI;Ying WANG;Aifu LIN

MOE Laboratory of Biosystem Homeostasis and Protection,College of Life Sciences,Zhejiang University,Hangzhou 310058,China;Cancer Center,Zhejiang University,Hangzhou 310058,China;Key Laboratory for Cell and Gene Engineering of Zhejiang Province,Hangzhou 310058,China;Chu Kochen Honors College of Zhejiang University,Hangzhou 310058,China;Breast Center of the First Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310003,China;International School of Medicine,International Institutes of Medicine,the Fourth Affiliated Hospital of Zhejiang University School of Medicine,Yiwu 322000,China;ZJU-QILU Joint Research Institute,Hangzhou 310058,China

浙江大学学报（英文版）（B辑：生物医学和生物技术）

[1]Zerui GAO;Xingyi LING;Chengyu SHI;Ying WANG;Aifu LIN-.Tumor immune checkpoints and their associated inhibitors)[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2022(10):823-843

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