Chu, Yanshuo;
Dai, Enyu;
Li, Yating;
Han, Guangchun;
Pei, Guangsheng;
Ingram, Davis R;
Thakkar, Krupa;
... Wang, Linghua; + view all
(2023)
Pan-cancer T cell atlas links a cellular stress response state to immunotherapy resistance.
Nature Medicine
, 29
(6)
pp. 1550-1562.
10.1038/s41591-023-02371-y.
Preview |
Text
nihms-2010124.pdf - Accepted Version Download (9MB) | Preview |
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, 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.
| Type: | Article |
|---|---|
| Title: | Pan-cancer T cell atlas links a cellular stress response state to immunotherapy resistance |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41591-023-02371-y |
| Publisher version: | https://doi.org/10.1038/s41591-023-02371-y |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, Medicine, Research & Experimental, Research & Experimental Medicine, TGF-BETA, TUMOR, LANDSCAPE, MECHANISMS, EXCLUSION |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10213405 |
Archive Staff Only
 |
View Item |
