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Journal of Zhejiang University SCIENCE B

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Tumor immune checkpoints and their associated inhibitors


Author(s):  Zerui Gao, Xingyi Ling, Chengyu Shi, Ying Wang, Aifu Lin

Affiliation(s):  MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University; more

Corresponding email(s):  linaifu@zju.edu.cn

Key Words:  Immune checkpoint; Immune checkpoint inhibitor; PD-L1; CTLA-4; LAG-3; TIGIT; B7 family


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Zerui Gao, Xingyi Ling, Chengyu Shi, Ying Wang, Aifu Lin. Tumor immune checkpoints and their associated inhibitors[J]. Journal of Zhejiang University Science B, 1998, -1(7): .

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Abstract: 
Immunological evasion is one of the defining characteristics of cancers, as the immune modification of an immune checkpoint confers immune evasion capabilities to tumor cells. Multiple immune checkpoints, 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. Immune checkpoint blockade (ICB) therapies targeting these checkpoint molecules have demonstrated significant clinical benefits. This is because antibody-based immune checkpoint 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 immune checkpoint 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 immune checkpoint 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 immune checkpoint molecules, focusing on their potential implications for cancer diagnostics and immunotherapy.

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