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(2024-01-31 23:53):
#paper doi: 10.1038/s41591-023-02371-y. Epub 2023 May 29.Pan-cancer T cell atlas links a cellular stress response state to immunotherapy resistance 。T细胞是肿瘤免疫中非常重要的存在,肿瘤细胞被发现之后,T细胞就会以指数方式增殖向效应T细胞和记忆T细胞分化,快速消灭外来病原体/肿瘤,但经历不断的抗原刺激和免疫抑制信号的干扰,一些T细胞也会进入疲软期,分化为功能丧失的状态,称为T细胞耗竭(TEX)。MD安德森癌症中心对T细胞状态的广泛多样性以及它们在复杂的肿瘤微环境中的关系和作用提供了更深入的了解,为理解癌症免疫治疗效果带来了新的视角。文章主要提出了一个新的概念:T细胞应激反应状态(T cell stress response state),是指当细胞面临不利环境或压力时触发的一系列变化,以保持细胞的稳态和适应环境。适度的应激刺激可以激活细胞的防御机制,促进修复和适应能力的提高。在肿瘤中,TSTR细胞可以被认为是一类“压力过大”的T细胞。但与TEX细胞的不同,T细胞是通过两条截然不同的途径分化为TEX细胞与TSTR细胞。新的T细胞类型的发现对指导之后的肿瘤免疫微环境分析很大的价值,值得对作者数据再次进行挖掘,例如得到新的细胞亚型signature。推荐给做肿瘤科研的小伙伴,值得一读。
Pan-cancer T cell atlas links a cellular stress response state to immunotherapy resistance
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Abstract:
Tumor-infiltrating T cells offer a promising avenue for cancer treatment, yet their states remain to be fully characterized. Here we present a single-cell atlas of T cells from 308,048 transcriptomes across 16 cancer types, uncovering previously undescribed T cell states and heterogeneous subpopulations of follicular helper, regulatory and proliferative T cells. We identified a unique stress response state, T, characterized by heat shock gene expression. T cells are detectable in situ in the tumor microenvironment across various cancer types, mostly within lymphocyte aggregates or potential tertiary lymphoid structures in tumor beds or surrounding tumor edges. T cell states/compositions correlated with genomic, pathological and clinical features in 375 patients from 23 cohorts, including 171 patients who received immune checkpoint blockade therapy. We also found significantly upregulated heat shock gene expression in intratumoral CD4/CD8 cells following immune checkpoint blockade treatment, particularly in nonresponsive tumors, suggesting a potential role of T cells in immunotherapy resistance. Our well-annotated T cell reference maps, web portal and automatic alignment/annotation tool could provide valuable resources for T cell therapy optimization and biomarker discovery.
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