Saravia Jordy, Chi Hongbo
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Oncogene. 2025 Jul;44(25):2011-2024. doi: 10.1038/s41388-025-03458-1. Epub 2025 Jun 4.
Regulatory T (T) cells play critical roles in maintaining immune tolerance and tissue homeostasis, but impede anti-tumor immunity. Recent work has established how T cells metabolically adapt within the tumor microenvironment (TME), and these adaptations frequently provide a functional advantage over effector T cells. Further, enhanced T cell function in the TME may contribute to the limited efficacy of current immunotherapies, especially immune checkpoint blockade (ICB). Here, we review recent progress in understanding mechanisms of T cell heterogeneity and function in tumors, with a particular focus on cellular metabolism as an underlying factor by which T cells are uniquely poised to thrive in the TME and contribute to tumorigenesis. We describe how cellular metabolism and nutrient or metabolic communication shape T cell lineage identity and function in the TME. We also discuss the interplay between ICB and T cell metabolism and function, and highlight current strategies targeting T cell metabolism specifically in the TME. Understanding metabolic control of intratumoral T cells provides excellent opportunities to uncover new or combination therapies for cancer.
调节性T（Treg）细胞在维持免疫耐受和组织稳态中发挥着关键作用，但会阻碍抗肿瘤免疫。最近的研究已经明确了Treg细胞在肿瘤微环境（TME）中如何进行代谢适应，并且这些适应通常比效应T细胞具有功能优势。此外，TME中Treg细胞功能的增强可能导致当前免疫疗法，尤其是免疫检查点阻断（ICB）的疗效有限。在这里，我们回顾了在理解肿瘤中Treg细胞异质性和功能机制方面的最新进展，特别关注细胞代谢这一潜在因素，通过该因素Treg细胞在TME中独特地具备茁壮成长并促进肿瘤发生的能力。我们描述了细胞代谢以及营养或代谢通讯如何塑造TME中Treg细胞的谱系特征和功能。我们还讨论了ICB与Treg细胞代谢和功能之间的相互作用，并重点介绍了目前专门针对TME中Treg细胞代谢的策略。了解肿瘤内Treg细胞的代谢调控为发现新的癌症治疗方法或联合治疗提供了绝佳机会。
