| Literature DB >> 31606264 |
Zeyu Chen1, Zhicheng Ji2, Shin Foong Ngiow1, Sasikanth Manne1, Zhangying Cai1, Alexander C Huang3, John Johnson4, Ryan P Staupe1, Bertram Bengsch1, Caiyue Xu5, Sixiang Yu6, Makoto Kurachi1, Ramin S Herati3, Laura A Vella7, Amy E Baxter1, Jennifer E Wu1, Omar Khan1, Jean-Christophe Beltra1, Josephine R Giles1, Erietta Stelekati1, Laura M McLane1, Chi Wai Lau1, Xiaolu Yang6, Shelley L Berger5, Golnaz Vahedi8, Hongkai Ji2, E John Wherry9.
Abstract
TCF-1 is a key transcription factor in progenitor exhausted CD8 T cells (Tex). Moreover, this Tex cell subset mediates responses to PD-1 checkpoint pathway blockade. However, the role of the transcription factor TCF-1 in early fate decisions and initial generation of Tex cells is unclear. Single-cell RNA sequencing (scRNA-seq) and lineage tracing identified a TCF-1+Ly108+PD-1+ CD8 T cell population that seeds development of mature Tex cells early during chronic infection. TCF-1 mediated the bifurcation between divergent fates, repressing development of terminal KLRG1Hi effectors while fostering KLRG1Lo Tex precursor cells, and PD-1 stabilized this TCF-1+ Tex precursor cell pool. TCF-1 mediated a T-bet-to-Eomes transcription factor transition in Tex precursors by promoting Eomes expression and drove c-Myb expression that controlled Bcl-2 and survival. These data define a role for TCF-1 in early-fate-bifurcation-driving Tex precursor cells and also identify PD-1 as a protector of this early TCF-1 subset.Entities:
Keywords: CD8 T cell exhaustion; PD-1; cancer; chronic infection; exhaustion; immunotherapy; transcriptional circuit
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Year: 2019 PMID： 31606264 PMCID： PMC6943829 DOI： 10.1016/j.immuni.2019.09.013
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745