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The discovery of immune checkpoint proteins has marked a major breakthrough in cancer immunotherapy. During cancer development and progression, tumor cells exploit multiple immune checkpoint pathways to evade immune surveillance. Immune checkpoint inhibitors (ICIs) have been developed to restore antitumor immunity by reactivating immune cells that are functionally suppressed within the tumor microenvironment. This review provides a comprehensive overview of the regulation and therapeutic targeting of immune checkpoint proteins in cancer, covering both classical checkpoints, including PD-1, PD-L1, and CTLA-4, and emerging targets such as LAG-3, TIM-3, TIGIT, BTLA, SIRP-α, CD200, ILT4, and CD24. In addition, we summarize current clinical advances and the therapeutic potential of approved and investigational ICIs, examine the mechanisms underlying ICI resistance, and discuss future strategies to overcome resistance, highlighting the mechanisms of action and their implications for future cancer treatment.
CHEN et al. (Mon,) studied this question.