Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
Department of Pathology and Immunology, Washington University, St. Louis, MO, USA.
Adv Exp Med Biol. 2021;1278:229-256. doi: 10.1007/978-981-15-6407-9_12.
Regulatory T cells (Tregs) are critical in maintaining immune homeostasis under various pathophysiological conditions. A growing body of evidence demonstrates that Tregs play an important role in cancer progression and that they do so by suppressing cancer-directed immune responses. Tregs have been targeted for destruction by exploiting antibodies against and small-molecule inhibitors of several molecules that are highly expressed in Tregs-including immune checkpoint molecules, chemokine receptors, and metabolites. To date, these strategies have had only limited antitumor efficacy, yet they have also created significant risk of autoimmunity because most of them do not differentiate Tregs in tumors from those in normal tissues. Currently, immune checkpoint inhibitor (ICI)-based cancer immunotherapies have revolutionized cancer treatment, but the resistance to ICI is common and the elevation of Tregs is one of the most important mechanisms. Therapeutic strategies that can selectively eliminate Tregs in the tumor (i.e. therapies that do not run the risk of causing autoimmunity by affecting normal tissue), are urgently needed for the development of cancer immunotherapies. This chapter discusses specific properties of human Tregs under the context of cancer and the various ways to target Treg for cancer immunotherapy.
调节性 T 细胞（Tregs）在各种病理生理条件下维持免疫稳态中起着关键作用。越来越多的证据表明，Tregs 在癌症进展中发挥重要作用，它们通过抑制针对癌症的免疫反应来实现这一作用。已经利用针对在 Tregs 中高度表达的几种分子（包括免疫检查点分子、趋化因子受体和代谢物）的抗体和小分子抑制剂来靶向破坏 Tregs。迄今为止，这些策略仅具有有限的抗肿瘤疗效，但它们也造成了严重的自身免疫风险，因为它们中的大多数都不能区分肿瘤中的 Tregs 和正常组织中的 Tregs。目前，基于免疫检查点抑制剂（ICI）的癌症免疫疗法已经彻底改变了癌症治疗，但对 ICI 的耐药性很常见，Tregs 的升高是最重要的机制之一。对于癌症免疫疗法的发展，迫切需要能够选择性地在肿瘤中消除 Tregs 的治疗策略（即不会通过影响正常组织而导致自身免疫的风险的疗法）。本章讨论了人类 Tregs 在癌症背景下的特定特性，以及针对 Treg 进行癌症免疫治疗的各种方法。
