Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
J Hematol Oncol. 2022 Aug 10;15(1):104. doi: 10.1186/s13045-022-01322-3.
Characterized by the expression of the critical transcription factor forkhead box protein P3, regulatory T (Treg) cells are an essential part of the immune system, with a dual effect on the pathogenesis of autoimmune diseases and cancer. Targeting Tregs to reestablish the proinflammatory and immunogenic tumor microenvironment (TME) is an increasingly attractive strategy for cancer treatment and has been emphasized in recent years. However, attempts have been significantly hindered by the subsequent autoimmunity after Treg ablation owing to systemic loss of their suppressive capacity. Cellular metabolic reprogramming is acknowledged as a hallmark of cancer, and emerging evidence suggests that elucidating the underlying mechanisms of how intratumoral Tregs acquire metabolic fitness and superior immunosuppression in the TME may contribute to clinical benefits. In this review, we discuss the common and distinct metabolic profiles of Tregs in peripheral tissues and the TME, as well as the differences between Tregs and other conventional T cells in their metabolic preferences. By focusing on the critical roles of different metabolic programs, such as glycolysis, oxidative phosphorylation, fatty acid oxidation, fatty acid synthesis, and amino acid metabolism, as well as their essential regulators in modulating Treg proliferation, migration, and function, we hope to provide new insights into Treg cell-targeted antitumor immunotherapies.
特征在于关键转录因子叉头框蛋白 P3 的表达，调节性 T（Treg）细胞是免疫系统的重要组成部分，对自身免疫性疾病和癌症的发病机制具有双重影响。靶向 Treg 以重新建立促炎和免疫原性肿瘤微环境（TME）是癌症治疗的一种越来越有吸引力的策略，近年来已得到强调。然而，由于系统性丧失其抑制能力，Treg 消融后随后发生自身免疫，这一尝试受到了显著阻碍。细胞代谢重编程被认为是癌症的标志，新出现的证据表明，阐明肿瘤内 Treg 在 TME 中获得代谢适应性和卓越免疫抑制作用的潜在机制可能有助于临床获益。在这篇综述中，我们讨论了外周组织和 TME 中 Treg 的常见和独特代谢特征，以及 Treg 在代谢偏好方面与其他常规 T 细胞的区别。通过关注不同代谢程序（如糖酵解、氧化磷酸化、脂肪酸氧化、脂肪酸合成和氨基酸代谢）以及调节 Treg 增殖、迁移和功能的关键调节剂的关键作用，我们希望为 Treg 细胞靶向抗肿瘤免疫疗法提供新的见解。
