Insights into antigen specific CD8+T cell exhaustion
CD8+T cells are the primary mediators of antigen-specific immune responses,with their functional states finely regulated by molecular mechanisms,playing a crucial role in tumor immunity.In recent years,CD8+T-cell-based cellular therapies(e.g.,TCR-T and CAR-T cell therapy)and immune checkpoint therapies that block PD-1 signaling pathway have achieved unprecedented success in clinical cancer treatments.However,the therapeutic effects of these immunotherapies are still limited,mainly due to immune resistance,with a significant factor being the functional exhaustion of tumor antigen-specific CD8+T cells.Consequently,a major focus and challenge in immunotherapy research is to understand the regulatory mechanisms behind this functional exhaustion and to develop intervention strategies and targets to enhance CD8+T cell effector functions.This article reviews the research progress in antitumor immune responses of CD8+T cells from three perspectives:The heterogeneity of exhausted CD8+T cells,their response to PD-1 immune checkpoint blockade(ICB),and their epigenetic characteristics.
CD8+T cell exhaustionImmune checkpoint blockade therapyExhausted T cell HeterogeneityEpigenetic characteristics
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