| First Author | Hanna BS | Year | 2021 |
| Journal | Immunity | Volume | 54 |
| Issue | 12 | Pages | 2825-2841.e10 |
| PubMed ID | 34879221 | Mgi Jnum | J:321662 |
| Mgi Id | MGI:6856546 | Doi | 10.1016/j.immuni.2021.11.004 |
| Citation | Hanna BS, et al. (2021) Interleukin-10 receptor signaling promotes the maintenance of a PD-1(int) TCF-1(+) CD8(+) T cell population that sustains anti-tumor immunity. Immunity 54(12):2825-2841.e10 |
| abstractText | 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(int) 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(int) TCF-1(+) CD8(+) T cells is regulated by cell-intrinsic IL-10R signaling, with implications for immunotherapy. |
