Schrödinger's T Cells: Molecular Insights Into Stemness and Exhaustion.
Schrödinger's T Cells: Molecular Insights Into Stemness and Exhaustion.
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DOI：
10.3389/fimmu.2021.725618
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发表时间：
2021
影响因子：
7.3
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Gonzalez NM;Zou D;Gu A;Chen W
T细胞干细胞和衰竭作为两个关键的对比现象共存于慢性抗原刺激过程中，如感染、移植、癌症和自身免疫。T细胞耗竭是指由慢性抗原暴露引起的效应子功能的进行性丧失。耗尽的T（TEX）细胞高度表达多种抑制性受体，并且在细胞增殖和细胞因子产生方面表现出严重缺陷。术语“T细胞干性”描述了T细胞的干细胞样行为，包括自我更新、多能性和功能持续性。众所周知，幼稚和一些记忆T细胞亚群具有干细胞样特性。在研究慢性感染和癌症中T细胞的彻底分化时，最近的研究强调了“耗尽的”T（TPEX）细胞的前体在其终末分化为TEX细胞之前的干性。临床上成功的用于癌症治疗的检查点阻断似乎激活抗肿瘤TPEX细胞，但不激活TEX细胞。在这里，我们讨论了T细胞干细胞和耗竭的转录和表观遗传调控，重点是如何利用系统免疫学来定义TPEX向TEX细胞转变的分子基础。我们提出了一个T细胞干细胞性和衰竭的“逐步模型”，其中干细胞性的丧失和衰竭进展是渐进的多步骤过程。我们提供了在移植环境中定义T细胞干细胞和衰竭所需的研究的观点，其中同种异体T细胞也长期暴露于同种异体抗原。更好地了解T细胞干细胞和衰竭将有助于开发新的免疫治疗策略。
T cell stemness and exhaustion coexist as two key contrasting phenomena during chronic antigen stimulation, such as infection, transplant, cancer, and autoimmunity. T cell exhaustion refers to the progressive loss of effector function caused by chronic antigen exposure. Exhausted T (TEX) cells highly express multiple inhibitory receptors and exhibit severe defects in cell proliferation and cytokine production. The term T cell stemness describes the stem cell-like behaviors of T cells, including self-renewal, multipotency, and functional persistence. It is well accepted that naïve and some memory T cell subsets have stem cell-like properties. When investigating the exhaustive differentiation of T cells in chronic infection and cancer, recent studies highlighted the stemness of “precursors of exhausted” T (TPEX) cells prior to their terminal differentiation to TEX cells. Clinically successful checkpoint blockades for cancer treatment appear to invigorate antitumor TPEX cells but not TEX cells. Here we discuss the transcriptional and epigenetic regulations of T cell stemness and exhaustion, with a focus on how systems immunology was and will be utilized to define the molecular basis underlying the transition of TPEX to TEX cells. We suggest a “stepwise model” of T cell stemness and exhaustion, in which loss of stemness and exhaustion progression are gradual multi-step processes. We provide perspectives on the research needed to define T cell stemness and exhaustion in the transplantation setting, in which allogenic T cells are also chronically exposed to alloantigens. A better understanding of T cell stemness and exhaustion will shed light on developing novel strategies for immunotherapies.
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影响因子：
32.4
作者：
Goronzy JJ;Weyand CM
通讯作者：
Weyand CM
影响因子：
30.5
作者：
Galletti G;De Simone G;Mazza EMC;Puccio S;Mezzanotte C;Bi TM;Davydov AN;Metsger M;Scamardella E;Alvisi G;De Paoli F;Zanon V;Scarpa A;Camisa B;Colombo FS;Anselmo A;Peano C;Polletti S;Mavilio D;Gattinoni L;Boi SK;Youngblood BA;Jones RE;Baird DM;Gostick E;Llewellyn-Lacey S;Ladell K;Price DA;Chudakov DM;Newell EW;Casucci M;Lugli E
通讯作者：
Lugli E
DOI：
10.1038/nrc3322
发表时间：
2012-10
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Gattinoni L;Klebanoff CA;Restifo NP
通讯作者：
Restifo NP
影响因子：
82.9
作者：
Gattinoni L;Lugli E;Ji Y;Pos Z;Paulos CM;Quigley MF;Almeida JR;Gostick E;Yu Z;Carpenito C;Wang E;Douek DC;Price DA;June CH;Marincola FM;Roederer M;Restifo NP
通讯作者：
Restifo NP
影响因子：
15.9
作者：
Baitsch, Lukas;Baumgaertner, Petra;Speiser, Daniel E.
通讯作者：
Speiser, Daniel E.