A unified atlas of CD8 T cell dysfunctional states in cancer and infection Journal Article
| Authors: | Pritykin, Y.; van der Veeken, J.; Pine, A. R.; Zhong, Y.; Sahin, M.; Mazutis, L.; Pe'er, D.; Rudensky, A. Y.; Leslie, C. S. |
| Article Title: | A unified atlas of CD8 T cell dysfunctional states in cancer and infection |
| Abstract: | CD8 T cells play an essential role in defense against viral and bacterial infections and in tumor immunity. Deciphering T cell loss of functionality is complicated by the conspicuous heterogeneity of CD8 T cell states described across experimental and clinical settings. By carrying out a unified analysis of over 300 assay for transposase-accessible chromatin sequencing (ATAC-seq) and RNA sequencing (RNA-seq) experiments from 12 studies of CD8 T cells in cancer and infection, we defined a shared differentiation trajectory toward dysfunction and its underlying transcriptional drivers and revealed a universal early bifurcation of functional and dysfunctional T cell states across models. Experimental dissection of acute and chronic viral infection using single-cell ATAC (scATAC)-seq and allele-specific single-cell RNA (scRNA)-seq identified state-specific drivers and captured the emergence of similar TCF1+ progenitor-like populations at an early branch point, at which functional and dysfunctional T cells diverge. Our atlas of CD8 T cell states will facilitate mechanistic studies of T cell immunity and translational efforts. © 2021 Elsevier Inc. |
| Keywords: | transcription factors; adoptive transfer; rna-seq; single cell; t cell exhaustion; atac-seq; computational integration; cut&run; t cell dysfunction; tcf1+ progenitor |
| Journal Title: | Molecular Cell |
| Volume: | 81 |
| Issue: | 11 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2021-01-01 |
| Start Page: | 2477 |
| End Page: | 2493.e10 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2021.03.045 |
| PUBMED: | 33891860 |
| PROVIDER: | scopus |
| PMCID: | PMC8454502 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 July 2021 -- Source: Scopus |
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