免疫检查点阻断 (ICB) 疗法可阻断 T 细胞上的抑制性受体，可有效恢复功能失调的 T 细胞反应。然而，大多数癌症对这些疗法没有反应，即使有反应，肿瘤也会获得耐药性。需要新的策略来拯救和招募跨患者群体和疾病状态的 T 细胞反应。在这篇综述中，我们定义了 T 细胞功能障碍的机制，重点关注关键转录因子 (TF) 网络。我们讨论了核心转录因子在 T 细胞功能和功能障碍中复杂且有时相互矛盾的作用。最后，我们回顾了使用小分子调节剂靶向 TF 的策略，这代表了一个具有挑战性但非常有前途的机会来调整 T 细胞反应以实现持续免疫。版权所有 © 2024。由 Elsevier Ltd 出版。

Immune checkpoint blockade (ICB) therapies, which block inhibitory receptors on T cells, can be efficacious in reinvigorating dysfunctional T cell responses. However, most cancers do not respond to these therapies and even in those that respond, tumors can acquire resistance. New strategies are needed to rescue and recruit T cell responses across patient populations and disease states. In this review, we define mechanisms of T cell dysfunction, focusing on key transcription factor (TF) networks. We discuss the complex and sometimes contradictory roles of core TFs in both T cell function and dysfunction. Finally, we review strategies to target TFs using small molecule modulators, which represent a challenging but highly promising opportunity to tune the T cell response toward sustained immunity.Copyright © 2024. Published by Elsevier Ltd.