Developmental Relationships of Four Exhausted CD8⁺ T Cell Subsets Reveals Underlying Transcriptional and Epigenetic Landscape Control Mechanisms.

ABSTRACT: CD8⁺ T cell exhaustion is a major barrier to current anti-cancer immunotherapies. Despite this, the developmental biology of exhausted CD8⁺ T cells (Tex) remains poorly defined, restraining improvement of strategies aimed at "re-invigorating" Tex cells. Here, we defined a four-cell-stage developmental framework for Tex cells. Two TCF1⁺ progenitor subsets were identified, one tissue restricted and quiescent and one more blood accessible, that gradually lost TCF1 as it divided and converted to a third intermediate Tex subset. This intermediate subset re-engaged some effector biology and increased upon PD-L1 blockade but ultimately converted into a fourth, terminally exhausted subset. By using transcriptional and epigenetic analyses, we identified the control

SUBMITTER: Beltra JC 

PROVIDER: S-EPMC8360766 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature