Dataset related to article "High-dimensional single cell analysis identifies stem-like cytotoxic CD8+ T cells infiltrating human tumors"

This record contains raw data related to article "High-dimensional single cell analysis identifies stem-like cytotoxic CD8+ T cells infiltrating human tumors" CD8⁺ T cells infiltrating tumors are largely dysfunctional, but whether a subset maintains superior functionality remains ill defined. By high-dimensional single cell analysis of millions of CD8⁺ T cells from 53 individuals with lung cancer, we defined those subsets that are enriched in tumors compared with cancer-free tissues and blood. Besides exhausted and activated cells, we identified CXCR5⁺ TIM-3^- CD8⁺ T cells with a partial exhausted phenotype, while retaining gene networks responsible for stem-like plasticity and cytotoxicity, as revealed by single cell sequencing of the whole transcriptome. Ex vivo, CXCR5⁺ TIM-3^- CD8⁺ T cells displayed enhanced self-renewal and multipotency compared with more differentiated subsets and were largely polyfunctional. Analysis of inhibitory and costimulatory receptors revealed PD-1, TIGIT, and CD27 as possible targets of immunotherapy. We thus demonstrate a hierarchy of differentiation in the context of T cell exhaustion in human cancer similar to that of chronically infected mice, which is further shown to disappear with disease progression.本数据集包含与论文《高维单细胞分析（high-dimensional single cell analysis）鉴定出浸润人类肿瘤的干细胞样细胞毒性CD8阳性T细胞（stem-like cytotoxic CD8⁺ T cells）》相关的原始数据。浸润肿瘤的CD8阳性T细胞（CD8⁺ T cells）大多呈功能失调状态，但目前尚不明确是否存在某一亚群仍能维持优异的功能。本研究通过对53例肺癌患者的数百万个CD8阳性T细胞（CD8⁺ T cells）开展高维单细胞分析，明确了相较于癌旁正常组织与外周血，在肿瘤中富集的CD8阳性T细胞亚群。除耗竭性与活化性CD8阳性T细胞外，本研究还通过全转录组单细胞测序（single cell sequencing of the whole transcriptome）分析，鉴定出一类呈部分耗竭表型的CXCR5阳性TIM-3阴性（CXCR5⁺ TIM-3^-）CD8阳性T细胞，该亚群仍保留了介导干细胞样可塑性与细胞毒性的基因调控网络。体外实验表明，相较于分化程度更高的T细胞亚群，此类CXCR5阳性TIM-3阴性CD8阳性T细胞具有更强的自我更新能力与多向分化潜能，且整体呈现多细胞因子分泌功能。对抑制性与共刺激受体的分析显示，PD-1、TIGIT与CD27可作为免疫治疗的潜在靶点。综上，本研究证实人类肿瘤中T细胞耗竭过程存在分化层级，该层级与慢性感染小鼠中的情况相似，且进一步研究发现该分化层级会随疾病进展而消失。