COX-2 Inhibitors Decrease Expression of PD-L1 in Colon Tumors and Increase the Influx of Type I Tumor-infiltrating Lymphocytes.

ABSTRACT: Colon cancer is initiated under inflammatory conditions associated with upregulation of immune checkpoint proteins. We evaluated immune modulation induced by nonsteroidal anti-inflammatory agents used for colon cancer prevention. Both celecoxib and naproxen inhibited polyp growth in APC Min mice. Treatment of mice with either drug significantly decreased PD-L1 expression on polyps in a dose-dependent manner (P < 0.0001 for both). The decrease in PD-L1 was associated with an influx of CD8+ T cells into polyps (P < 0.0001, celecoxib; P = 0.048, naproxen) compared with lesions from untreated animals and correlated with disease control. Naproxen is a nonselective inhibitor of both COX-1 and COX-2, and we questioned the role of the different cyclooxygenases in PD-L1 regulation. Silencing either

SUBMITTER: Cecil DL 

PROVIDER: S-EPMC8983455 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature