Tumor immune checkpoints and their associated inhibitors.

Zerui Gao; Xingyi Ling; Chengyu Shi; Ying Wang; Aifu Lin

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Tumor immune checkpoints and their associated inhibitors.

Author: Zerui GAO ¹ ; Xingyi LING ¹ ; Chengyu SHI ¹ ; Ying WANG ¹ ; Aifu LIN ²
Author Information

1. MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
2. MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou 310058, China. linaifu@zju.edu.cn.
Publication Type:Review
Keywords: B7 family; Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4); Immune checkpoint; Immune checkpoint inhibitor; Lymphocyte activation gene-3 (LAG-3); Programmed cell death-ligand 1 (PD-L1); T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT)
MeSH: Apoptosis Regulatory Proteins; CTLA-4 Antigen/therapeutic use*; Epigenesis, Genetic; Humans; Immunotherapy; Neoplasms/therapy*; Programmed Cell Death 1 Receptor/therapeutic use*
From: Journal of Zhejiang University. Science. B 2022;23(10):823-843
CountryChina
Language:English
Abstract: 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.