Pan-cancer T cell atlas links a cellular stress response state to immunotherapy resistance

被引：0
作者：
Yanshuo Chu
Enyu Dai
Yating Li
Guangchun Han
Guangsheng Pei
Davis R. Ingram
Krupa Thakkar
Jiang-Jiang Qin
Minghao Dang
Xiuning Le
Can Hu
Qing Deng
Ansam Sinjab
Pravesh Gupta
Ruiping Wang
Dapeng Hao
Fuduan Peng
Xinmiao Yan
Yunhe Liu
Shumei Song
Shaojun Zhang
John V. Heymach
Alexandre Reuben
Yasir Y. Elamin
Melissa P. Pizzi
Yang Lu
Rossana Lazcano
Jian Hu
Mingyao Li
Michael Curran
Andrew Futreal
Anirban Maitra
Amir A. Jazaeri
Jaffer A. Ajani
Charles Swanton
Xiang-Dong Cheng
Hussein A. Abbas
Maura Gillison
Krishna Bhat
Alexander J. Lazar
Michael Green
Kevin Litchfield
Humam Kadara
Cassian Yee
Linghua Wang
机构：
[1] The University of Texas MD Anderson Cancer Center,Department of Genomic Medicine
[2] The University of Texas MD Anderson Cancer Center,Department of Melanoma Medical Oncology
[3] The University of Texas MD Anderson Cancer Center,Department of Translational Molecular Pathology
[4] University College London Cancer Institute,Tumour Immunogenomics and Immunosurveillance Laboratory
[5] Cancer Hospital of the University of Chinese Academy of Sciences,Department of Gastric Surgery
[6] Zhejiang Cancer Hospital,Institute of Basic Medicine and Cancer
[7] Chinese Academy of Sciences,Department of Thoracic/Head and Neck Medical Oncology
[8] The University of Texas MD Anderson Cancer Center,Department of Lymphoma and Myeloma
[9] The University of Texas MD Anderson Cancer Center,Department of Gastrointestinal Medical Oncology
[10] The University of Texas MD Anderson Cancer Center,Department of Nuclear Medicine
[11] The University of Texas MD Anderson Cancer Center,Department of Human Genetics
[12] Emory School of Medicine,Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine
[13] University of Pennsylvania,Department of Immunology
[14] The University of Texas MD Anderson Cancer Center,Department of Pathology
[15] The University of Texas MD Anderson Cancer Center,Department of Gynecologic Oncology and Reproductive Medicine
[16] The University of Texas MD Anderson Cancer Center,Cancer Evolution and Genome Instability Laboratory
[17] The Francis Crick Institute,Cancer Research UK Lung Cancer Centre of Excellence
[18] University College London Cancer Institute,Department of Leukemia
[19] The University of Texas MD Anderson Cancer Center,undefined
[20] The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences,undefined
来源：
Nature Medicine | 2023年 / 29卷
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摘要：
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, TSTR, characterized by heat shock gene expression. TSTR 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 TSTR 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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页码：1550 / 1562
页数：12
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