STTT：周芳芳/张龙/虞伟星等系统总结克服T细胞耗竭突破与挑战

Core Viewpoint - T cell exhaustion is a prevalent phenomenon in chronic infections and tumor microenvironments, significantly impairing the effectiveness of anti-tumor and anti-viral immunity [2][4][6]. Group 1: Mechanisms of T Cell Exhaustion - Key external factors leading to T cell exhaustion include persistent antigen exposure, immune checkpoint signaling, and cytokine environments [2][4]. - Internal changes such as metabolic alterations, epigenetic modifications, and transcriptional reprogramming also contribute to T cell dysfunction [2][4][6]. - T cell exhaustion can be seen as a complex and multifaceted process that involves both external immune microenvironment factors and internal cellular changes [4][5]. Group 2: Emerging Therapies - New therapies targeting T cell exhaustion aim to restore immune function and enhance anti-tumor and anti-viral immunity, including immune checkpoint inhibitors, cytokine therapies, metabolic reprogramming, and cell therapies [2][6]. - Despite advancements, challenges remain in reversing T cell exhaustion, such as patient variability, resistance, and potential side effects [2][6]. Group 3: Future Research Directions - Future research should focus on elucidating the remaining mysteries of T cell exhaustion, particularly in the context of complex disease microenvironments, and developing more precise and personalized therapies [6][20]. - The review emphasizes the biological basis of T cell exhaustion and therapeutic interventions that can revitalize exhausted T cells and restore their effector functions [6][17].