Plasmacytoid dendritic cells regulate colitis-associated tumorigenesis by controlling myeloid-derived suppressor cell infiltration. (28th November 2020)

• Record Type: Journal Article
• Authors: Hong, Eun-Hye; Cho, Jaewon; Ahn, Jae-hee; Kwon, Bo-Eun; Kweon, Mi-Na; Seo, Sang-Uk; Yoon, Byung-Il; Chang, Sun-Young; Ko, Hyun-Jeong
• Is Part Of: Cancer letters. Volume 493(2020)
• Page Start: 102
• Page End: 112
• Publication Date: 2020-11-28
• Subjects: Colorectal cancer -- Plasmacytoid dendritic cell -- Myeloid-derived suppressor cell -- Toll-like receptor; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2020.08.007
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Toll-like receptor (TLR)3 and TLR7 are important for stimulating plasmacytoid dendritic cells (pDCs), which secrete type I interferon. Mice deficient for TLR3 and TLR7 (TLR3 −/− TLR7 −/− ) reportedly exhibit deteriorated colitis because of impaired pDCs. However, the role of pDCs in tumorigenesis-associated inflammation progression has not been studied. We treated wild-type or TLR3 −/− TLR7 −/− mice with dextran sulfate sodium (DSS) and/or azoxymethane (AOM) and examined colon mucosa, measured body weight and colon length of mice, and examined pDC and myeloid-derived suppressor cell (MDSC) accumulation. Further, we depleted pDCs in AOM/DSS-treated wild-type mice by treating them with anti-PDCA-1 antibodies. We found that MDSCs significantly increased, while pDCs decreased in TLR3 −/− TLR7 −/− mice. Moreover, TLR3 −/− TLR7 −/− mice developed colitis-associated colon cancer following AOM/DSS treatment. Additionally, we showed that a defect in TLR7 of pDCs is responsible for the aggravation of colitis-associated colon cancer. Further, we showed that TLR7 ligand mitigates colitis-associated colon cancer. Collectively, our results demonstrate that gut pDCs play a crucial role in reducing colorectal cancer development via the regulation of infiltrating MDSCs. Highlights: We found that MDSC number significantly increased, while pDCs decreased in TLR3 −/− TLR7 −/− mice. Additionally, defect in TLR7s of pDCs is responsible for the aggravation of colitis-associated colon cancer. And we also show TLR7 ligand mitigate the colitis-associated colon cancer.