| First Author | Geels SN | Year | 2024 |
| Journal | Cancer Cell | Volume | 42 |
| Issue | 6 | Pages | 1051-1066.e7 |
| PubMed ID | 38861924 | Mgi Jnum | J:349941 |
| Mgi Id | MGI:7660325 | Doi | 10.1016/j.ccell.2024.05.013 |
| Citation | Geels SN, et al. (2024) Interruption of the intratumor CD8(+) T cell:Treg crosstalk improves the efficacy of PD-1 immunotherapy. Cancer Cell 42(6):1051-1066.e7 |
| abstractText | PD-1 blockade unleashes potent antitumor activity in CD8(+) T cells but can also promote immunosuppressive T regulatory (Treg) cells, which may worsen the response to immunotherapy. Tumor-Treg inhibition is a promising strategy to improve the efficacy of checkpoint blockade immunotherapy; however, our understanding of the mechanisms supporting tumor-Tregs during PD-1 immunotherapy is incomplete. Here, we show that PD-1 blockade increases tumor-Tregs in mouse models of melanoma and metastatic melanoma patients. Mechanistically, Treg accumulation is not caused by Treg-intrinsic inhibition of PD-1 signaling but depends on an indirect effect of activated CD8(+) T cells. CD8(+) T cells produce IL-2 and colocalize with Tregs in mouse and human melanomas. IL-2 upregulates the anti-apoptotic protein ICOS on tumor-Tregs, promoting their accumulation. Inhibition of ICOS signaling before PD-1 immunotherapy improves control over immunogenic melanoma. Thus, interrupting the intratumor CD8(+) T cell:Treg crosstalk represents a strategy to enhance the therapeutic efficacy of PD-1 immunotherapy. |
