Nimesulide inhibits IFN-gamma-induced programmed death-1-ligand 1 surface expression in breast cancer cells by COX-2 and PGE2 independent mechanisms.
It is now well established that increased programmed death-1-ligand 1 (PD-L1) surface expression in cancer cells and the resultant T cell suppression contribute to cancer cell immune evasion. Blockade of PD-L1 function has been shown to stimulate anti-cancer immunity. Therefore, compounds that can down-regulate PD-L1 surface expression in cancer cells may serve as novel immune modulators to promote cancer cell-reactive immune responses. In the present study, we examined the effects of nimesulide, a selective COX-2 inhibitor, on PD-L1 surface expression in breast cancer cells by flow cytometry. We demonstrated that nimesulide was able to inhibit IFN-gamma-induced PD-L1 surface expression in breast cancer cells. However, our data indicate that the inhibitory effects of nimesulide appear to be independent of COX-2/PGE2 signaling. Since nimesulide also exhibits anti-tumor activities by inducing cancer cell apoptosis and inhibiting cancer cell proliferation, our findings suggest that nimesulide may represent a new class of chemotherapeutic agents that possess dual functions to inhibit cancer cell growth and promote cancer cell immune responses.
Liang
Mei
M
Center for Biomedical Research, University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA.
Yang
Hui
H
Fu
Jian
J
D015703:Antigens, CD / Q000096:biosynthesis / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D060890:B7-H1 Antigen; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*
D015703:Antigens, CD; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D004791:Enzyme Inhibitors; D013449:Sulfonamides; D007371:Interferon-gamma; D051546:Cyclooxygenase 2; D015232:Dinoprostone; C012655:nimesulide