Exhaustion-associated regulatory regions in CD8 <sup>+</sup> tumor-infiltrating T cells
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- Giuliana P. Mognol
- Division of Signaling and Gene Expression, La Jolla Institute, La Jolla, CA 92037;
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- Roberto Spreafico
- Signaling Systems Laboratory, University of California, Los Angeles, CA 90095;
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- Victor Wong
- Division of Signaling and Gene Expression, La Jolla Institute, La Jolla, CA 92037;
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- James P. Scott-Browne
- Division of Signaling and Gene Expression, La Jolla Institute, La Jolla, CA 92037;
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- Susan Togher
- Division of Signaling and Gene Expression, La Jolla Institute, La Jolla, CA 92037;
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- Alexander Hoffmann
- Signaling Systems Laboratory, University of California, Los Angeles, CA 90095;
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- Patrick G. Hogan
- Division of Signaling and Gene Expression, La Jolla Institute, La Jolla, CA 92037;
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- Anjana Rao
- Division of Signaling and Gene Expression, La Jolla Institute, La Jolla, CA 92037;
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- Sara Trifari
- Division of Signaling and Gene Expression, La Jolla Institute, La Jolla, CA 92037;
書誌事項
- 公開日
- 2017-03-10
- 権利情報
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- http://www.pnas.org/site/misc/userlicense.xhtml
- DOI
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- 10.1073/pnas.1620498114
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:title>Significance</jats:title> <jats:p> Cancer cells can be recognized and attacked by CD8 <jats:sup>+</jats:sup> cytolytic T cells, but tumor-infiltrating T cells often become functionally incompetent (“exhausted”) and fail to destroy tumor cells. We show that T-cell exhaustion requires antigen recognition by tumor-infiltrating T cells. By examining the transcriptional and chromatin accessibility profiles of antigen-reactive and -unreactive tumor-infiltrating cells, we confirm our previous conclusion that the transcription factor NFAT promotes CD8 <jats:sup>+</jats:sup> T-cell exhaustion and we identify Nr4a transcription factors as new targets for future investigation. We show that anti–PD-L1 treatment, a clinically relevant checkpoint blockade therapy that counteracts T-cell exhaustion, has modest but functionally important effects on gene expression in exhausted cells, without causing major changes in patterns of chromatin accessibility. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 114 (13), E2776-, 2017-03-10
Proceedings of the National Academy of Sciences