RT Journal Article
SR Electronic
T1 A unified atlas of CD8 T cell dysfunctional states in cancer and infection
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.25.220673
DO 10.1101/2020.07.25.220673
A1 Pritykin, Yuri
A1 van der Veeken, Joris
A1 Pine, Allison
A1 Zhong, Yi
A1 Sahin, Merve
A1 Mazutis, Linas
A1 Pe’er, Dana
A1 Rudensky, Alexander
A1 Leslie, Christina
YR 2020
UL http://biorxiv.org/content/early/2020/07/26/2020.07.25.220673.abstract
AB 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 different experimental and clinical settings. By carrying out a unified analysis of over 300 ATAC-seq and RNA-seq experiments from twelve independent studies of CD8 T cell dysfunction in cancer and infection we defined a shared differentiation trajectory towards terminal dysfunction and its underlying transcriptional drivers and revealed a universal early bifurcation of functional and dysfunctional T cell activation states across models. Experimental dissection of acute and chronic viral infection using scATAC-seq and allele-specific scRNA-seq identified state-specific transcription factors and captured the early emergence of highly similar TCF1+ progenitor-like populations at an early branch point, at which epigenetic features of functional and dysfunctional T cells diverge. Our atlas of CD8 T cell states will facilitate mechanistic studies of T cell immunity and translational efforts.Competing Interest StatementThe authors have declared no competing interest.