Department of Microbiology & Immunology Melbourne, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia.
Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany.
Nat Rev Immunol. 2020 Feb;20(2):128-136. doi: 10.1038/s41577-019-0223-7. Epub 2019 Oct 7.
Cytotoxic T cell immunity in response to chronic infections and tumours is maintained by a specialized population of CD8 T cells that exhibit hallmarks of both exhausted and memory cells and give rise to terminally differentiated exhausted effector cells that contribute to viral or tumour control. Importantly, recent work suggests these cells, which we refer to as 'precursor exhausted' T (T) cells, are responsible for the proliferative burst that generates effector T cells in response to immune checkpoint blockade targeting programmed cell death 1 (PD1), and increased T cell frequencies have recently been linked to increased patient survival. We believe the recent discovery of T cells not only represents a paradigm shift in our understanding of the mechanisms that maintain CD8 T cell responses in chronic infections and tumours but also opens up unexpected avenues for the development of new and innovative therapeutic approaches. In this Opinion article, we discuss the differentiation and function of T cells and suggest that targeting these cells may be key for successful immunotherapy.
针对慢性感染和肿瘤，细胞毒性 T 细胞免疫由一群具有耗竭细胞和记忆细胞特征的 CD8 T 细胞来维持，这些细胞最终分化为耗竭效应细胞，有助于控制病毒或肿瘤。重要的是，最近的研究表明，这些细胞，我们称之为“前体细胞耗竭”T（T）细胞，负责增殖爆发，产生效应 T 细胞对程序性细胞死亡 1（PD1）的免疫检查点阻断的反应，并且最近已经证明增加 T 细胞频率与增加患者的生存相关。我们认为，最近对 T 细胞的发现不仅代表了我们对维持慢性感染和肿瘤中 CD8 T 细胞反应的机制的理解的范式转变，而且还为开发新的创新治疗方法开辟了意想不到的途径。在这篇观点文章中，我们讨论了 T 细胞的分化和功能，并提出靶向这些细胞可能是成功免疫治疗的关键。
