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Developmental Relationships of Four Exhausted CD8+ T Cell Subsets Reveals Underlying Transcriptional and Epigenetic Landscape Control Mechanisms.
- Source :
-
Immunity (10747613) . May2020, Vol. 52 Issue 5, p825-825. 1p. - Publication Year :
- 2020
-
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 mechanisms underlying subset transitions and defined a key interplay between TCF1, T-bet, and Tox in the process. These data reveal a four-stage developmental hierarchy for Tex cells and define the molecular, transcriptional, and epigenetic mechanisms that could provide opportunities to improve cancer immunotherapy. • Ly108 and CD69 define four Tex subsets linked in a hierarchical developmental pathway • Two TCF1+ subsets, effector-like and terminally exhausted subsets, are identified • Key transcriptional, epigenetic, and biological changes define subset transitions • TCF1, T-bet, and Tox coordinate Tex subset development and dynamics Beltra et al. define a hierarchical developmental pathway for CD8+ T cell exhaustion, revealing four stages and multistep transcriptional and epigenetic dynamics underlying subset transitions and subset-associated biological changes. [ABSTRACT FROM AUTHOR]
- Subjects :
- *T cells
*DEVELOPMENTAL biology
*EPIGENETICS
*BIOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 10747613
- Volume :
- 52
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Immunity (10747613)
- Publication Type :
- Academic Journal
- Accession number :
- 143232063
- Full Text :
- https://doi.org/10.1016/j.immuni.2020.04.014