Tissue-resident T cells in Clinical Response and Immune-related Adverse Events of Immune Checkpoint Blockade.

IF 10 1区 医学 Q1 ONCOLOGY Clinical Cancer Research Pub Date : 2024-10-15 DOI:10.1158/1078-0432.ccr-23-3296
Ye Zhao,Kai W Wucherpfennig
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Abstract

T cell surveillance of tissues is spatially organized: circulating memory T cells perform surveillance of secondary lymphoid organs while tissue-resident memory T cells act as sentinels in barrier tissues. In the context of infection, tissue-resident memory T cells survive long term in barrier tissues and are poised to respond to re-encounter of infectious agents. The activity of such tissue-resident T cells is regulated by the PD-1 and CTLA-4 inhibitory receptors targeted by cancer immunotherapies. This review investigates the hypothesis that T cells with a tissue residency program play an important role in both protective anti-tumor immunity and immune-related adverse events (irAEs) of immune checkpoint blockade (ICB). A series of translational studies have demonstrated that a higher density of tissue-resident T cells within tumors is associated with favorable survival outcomes in a diverse range of cancer types. Tissue-resident T cells have also been implicated in clinical response to immune checkpoint blockade, and dynamic tracking of T cell populations in pre- and on-treatment tumor samples demonstrated that T cells with a tissue residency program responded early to ICB. Investigation of colitis and dermatitis as examples of irAEs demonstrated that tissue-resident memory T cells were reactivated at these epithelial sites, resulting in a highly cytotoxic state and secretion of inflammatory cytokines IFNγ and TNFα. It will therefore be important to consider how a tissue residency program can be enhanced to promote T cell-mediated tumor immunity while preventing the development of irAEs.
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免疫检查点阻断疗法临床反应和免疫相关不良事件中的组织驻留 T 细胞
T 细胞对组织的监控是有空间组织的:循环记忆 T 细胞对次级淋巴器官进行监控,而组织驻留记忆 T 细胞则在屏障组织中充当哨兵。在感染的情况下,组织驻留记忆 T 细胞在屏障组织中长期存活,并随时准备对再次遇到的感染病原体做出反应。这种组织驻留记忆 T 细胞的活性受癌症免疫疗法靶向的 PD-1 和 CTLA-4 抑制受体调控。本综述探讨了一个假设,即具有组织驻留程序的 T 细胞在保护性抗肿瘤免疫和免疫检查点阻断(ICB)的免疫相关不良事件(irAEs)中发挥着重要作用。一系列转化研究表明,肿瘤内组织驻留 T 细胞的高密度与多种癌症类型的有利生存结果相关。组织驻留 T 细胞还与免疫检查点阻断疗法的临床反应有关,对治疗前和治疗中肿瘤样本中 T 细胞群的动态追踪表明,具有组织驻留程序的 T 细胞对 ICB 早有反应。以结肠炎和皮炎为例进行的irAEs研究表明,组织驻留记忆T细胞在这些上皮部位被重新激活,导致高度细胞毒性状态并分泌炎性细胞因子IFNγ和TNFα。因此,重要的是要考虑如何加强组织驻留程序,以促进 T 细胞介导的肿瘤免疫,同时防止发生 irAEs。
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来源期刊
Clinical Cancer Research
Clinical Cancer Research 医学-肿瘤学
CiteScore
20.10
自引率
1.70%
发文量
1207
审稿时长
2.1 months
期刊介绍: Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.
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