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Subsets of exhausted CD8+T cells differentially mediate tumor control and respond to checkpoint blockade
- Source :
- Nature Immunology; March 2019, Vol. 20 Issue: 3 p326-336, 11p
- Publication Year :
- 2019
-
Abstract
- T cell dysfunction is a hallmark of many cancers, but the basis for T cell dysfunction and the mechanisms by which antibody blockade of the inhibitory receptor PD-1 (anti-PD-1) reinvigorates T cells are not fully understood. Here we show that such therapy acts on a specific subpopulation of exhausted CD8+tumor-infiltrating lymphocytes (TILs). Dysfunctional CD8+TILs possess canonical epigenetic and transcriptional features of exhaustion that mirror those seen in chronic viral infection. Exhausted CD8+TILs include a subpopulation of ‘progenitor exhausted’ cells that retain polyfunctionality, persist long term and differentiate into ‘terminally exhausted’ TILs. Consequently, progenitor exhausted CD8+TILs are better able to control tumor growth than are terminally exhausted T cells. Progenitor exhausted TILs can respond to anti-PD-1 therapy, but terminally exhausted TILs cannot. Patients with melanoma who have a higher percentage of progenitor exhausted cells experience a longer duration of response to checkpoint-blockade therapy. Thus, approaches to expand the population of progenitor exhausted CD8+T cells might be an important component of improving the response to checkpoint blockade.
Details
- Language :
- English
- ISSN :
- 15292908 and 15292916
- Volume :
- 20
- Issue :
- 3
- Database :
- Supplemental Index
- Journal :
- Nature Immunology
- Publication Type :
- Periodical
- Accession number :
- ejs48542775
- Full Text :
- https://doi.org/10.1038/s41590-019-0312-6