TCF-1-centered transcriptional network drives an effector versus exhausted CD8 T cell fate decision

By Zeyu Chen, Zhicheng Ji, S. Ngiow, Sasikanth Manne, Zhangying Cai, Alexander C. Huang, John L. Johnson, Ryan P. Staupe, Bertram Bengsch, Caiyue Xu and 17 more. Immunity, 2019

616 citations recorded by the source corpus.

Summary 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 early during chronic infection that seeds development of mature Tex cells. 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.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/1e1f4a96b81e59a6265771eac1d00d009fa26359

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In Immunology

1. Zemin Zhang
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Citations in the corpus

• Pan-cancer single-cell landscape of tumor-infiltrating T cells (2021, background): “A major population was terminal Tex cells, which exhibited higher expression of the gene ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1), which is related to terminal differentiation (22, 23).”
• Acquired Resistance to Immune Checkpoint Inhibitors (2020, background): “…duration of response data among different tumor types (Antonia et al., 2019; Armand et al., 2018; Balar et al., 2018; Burtness et al., 2019; Chen et al., 2019a; Cohen et al., 2019; Fehrenbacher et al., 2018; Fradet et al., 2019; Garon et al., 2019; Hamid et al., 2019; Herbst et al., 2016;…”