Insights into antigen specific CD8+ T cell exhaustion

Abstract

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.

Keywords

• cd8+ t cell exhaustion
• immune checkpoint blockade therapy
• exhausted t cell heterogeneity
• epigenetic characteristics