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_STR, characterized by heat shock gene expression. T_STR 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_STR 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.

肿瘤浸润 T 细胞为癌症治疗提供了一种有希望的途径，但它们的状态仍有待充分表征。在这里，我们展示了来自 16 种癌症类型的 308,048 个转录组的 T 细胞单细胞图谱，揭示了以前未描述的 T 细胞状态以及滤泡辅助、调节和增殖 T 细胞的异质亚群。我们确定了一种独特的应激反应状态 T _STR，其特征是热休克基因表达。T- _STR在各种癌症类型的肿瘤微环境中都可以原位检测到细胞，主要是在肿瘤床或肿瘤边缘周围的淋巴细胞聚集体或潜在的三级淋巴结构内。T 细胞状态/组成与 23 个队列的 375 名患者的基因组、病理和临床特征相关，其中包括 171 名接受免疫检查点阻断治疗的患者。我们还发现，免疫检查点阻断治疗后，肿瘤内 CD4/CD8 ⁺细胞中的热休克基因表达显着上调，特别是在无反应的肿瘤中，这表明 T _{STR的潜在作用}细胞对免疫治疗产生耐药性。我们注释完善的 T 细胞参考图、门户网站和自动对齐/注释工具可以为 T 细胞治疗优化和生物标志物发现提供宝贵的资源。