Hanna, Bola S. and Llao-Cid, Laura and Iskar, Murat and Roessner, Philipp M. and Klett, Lara C. and Wong, John K. L. and Paul, Yashna and Ioannou, Nikolaos and Ozturk, Selcen and Mack, Norman and Kalter, Verena and Colomer, Dolors and Campo, Elias and Bloehdorn, Johannes and Stilgenbauer, Stephan and Dietrich, Sascha and Schmidt, Manfred and Gabriel, Richard and Rippe, Karsten and Feuerer, Markus and Ramsay, Alan G. and Lichter, Peter and Zapatka, Marc and Seiffert, Martina (2021) Interleukin-10 receptor signaling promotes the maintenance of a PD-1(i)(nt) TCF-1(+) CD8(+) T cell population that sustains anti-tumor immunity. IMMUNITY, 54 (12). 2825-+. ISSN 1074-7613, 1097-4180
Full text not available from this repository. (Request a copy)Abstract
T cell exhaustion limits anti-tumor immunity and responses to immunotherapy, Here, we explored the microenvironmental signals regulating T cell exhaustion using a model of chronic lymphocytic leukemia (CLL). Single-cell analyses identified a subset of PD-1(hi), functionally impaired CD8(+) T cells that accumulated in secondary lymphoid organs during disease progression and a functionally competent PD-1(int) subset. Frequencies of PD-1(i)(nt) TCF-1(+) CD8(+) T cells decreased upon Il10rb or Stat3 deletion, leading to accumulation of PD-1(hi) cells and accelerated tumor progression. Mechanistically, inhibition of IL-10R signaling altered chromatin accessibility and disrupted cooperativity between the transcription factors NFAT and AP-1, promoting a distinct NFAT-associated program. Low IL10 expression or loss of IL-10R-STAT3 signaling correlated with increased frequencies of exhausted CD8(+) T cells and poor survival in CLL and in breast cancer patients, Thus, balance between PD-1(hi), exhausted CD8(+) T cells and functional PD-1(i)(nt) TCF-1(+) CD8(+) T cells is regulated by cell-intrinsic IL-10R signaling, with implications for immunotherapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHRONIC LYMPHOCYTIC-LEUKEMIA; CHRONIC VIRAL-INFECTION; R/BIOCONDUCTOR PACKAGE; EPIGENETIC LANDSCAPE; CHECKPOINT BLOCKADE; MOUSE MODEL; IL-10; EXHAUSTION; EXPRESSION; SUBSETS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Sep 2022 12:41 |
| Last Modified: | 20 Sep 2022 12:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47669 |
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