| First Author | Poschel DB | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 10 | Pages | 114819 |
| PubMed ID | 39368087 | Mgi Jnum | J:358057 |
| Mgi Id | MGI:7779401 | Doi | 10.1016/j.celrep.2024.114819 |
| Citation | Poschel DB, et al. (2024) PD-L1 restrains PD-1(+)Nrp1(lo) Treg cells to suppress inflammation-driven colorectal tumorigenesis. Cell Rep 43(10):114819 |
| abstractText | T cells function not only as an essential component of host cancer immunosurveillance but also as a regulator of colonic inflammation, a process that promotes colorectal cancer. Programmed death-ligand 1 (PD-L1) is a T cell-negative regulator, but its role in regulation of T cell functions in the context of colorectal cancer is unknown. We report that global deletion of Cd274 results in increased colonic inflammation, PD-1(+) T cells, and inflammation-driven colorectal tumorigenesis in mice. Single-cell RNA sequencing (scRNA-seq) analysis revealed that PD-L1 suppresses subpopulations of programmed cell death protein 1 (PD-1)(+)Nrp1(lo) regulatory T (Treg) cells and interleukin (IL) 6(+) neutrophils in colorectal tumor. Treg cells produce transforming growth factor (TGF) beta to recruit IL6(+) neutrophils. Neutrophils produce IL6 to inhibit activation of tumor-specific cytotoxic T lymphocytes (CTLs) and primary CTLs. Accordingly, IL6 blockade immunotherapy increases CTL activation and suppresses colon tumor growth in vivo. Our findings determine that PD-L1 restrains PD-1(+)Nrp1(lo)TGFbeta(+) Treg cells to suppress IL6(+) neutrophil tumor recruitment to sustain CTL activation to control inflammation-driven colorectal tumorigenesis. |
