| First Author | Mazet JM | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 321 |
| PubMed ID | 36658158 | Mgi Jnum | J:339513 |
| Mgi Id | MGI:7427975 | Doi | 10.1038/s41467-023-35948-9 |
| Citation | Mazet JM, et al. (2023) IFNgamma signaling in cytotoxic T cells restricts anti-tumor responses by inhibiting the maintenance and diversity of intra-tumoral stem-like T cells. Nat Commun 14(1):321 |
| abstractText | IFNgamma is an immune mediator with concomitant pro- and anti-tumor functions. Here, we provide evidence that IFNgamma directly acts on intra-tumoral CD8 T cells to restrict anti-tumor responses. We report that expression of the IFNgamma receptor beta chain (IFNgammaR2) in CD8 T cells negatively correlates with clinical responsiveness to checkpoint blockade in metastatic melanoma patients, suggesting that the loss of sensitivity to IFNgamma contributes to successful antitumor immunity. Indeed, specific deletion of IFNgammaR in CD8 T cells promotes tumor control in a mouse model of melanoma. Chronic IFNgamma inhibits the maintenance, clonal diversity and proliferation of stem-like T cells. This leads to decreased generation of T cells with intermediate expression of exhaustion markers, previously associated with beneficial anti-tumor responses. This study provides evidence of a negative feedback loop whereby IFNgamma depletes stem-like T cells to restrict anti-tumor immunity. Targeting this pathway might represent an alternative strategy to enhance T cell-based therapies. |
