Objectives: In this study, it was aimed to investigate how the effects of Mesenchymal stem cells (MSCs) on the antitumor properties of NK-92 cells change with programmed death-ligand-1 (PD-L1) blocking antibodies. Methods: NK-92 cells were co-cultured with MDA-MB-231 breast tumor cells and MSCs. To evaluate the effect of antiPD-L1 antibodies, cells were cultured for 48 hours with and without the addition of 1, 5, and 10 µg/ml anti PD-L1 antibody. IFN-?, TNF-?, IL-10 and IDO levels of medium supernatants were determined by ELISA. CCK-8 kit was used to evaluate cytotoxic activity. Results: IFN-? and TNF-? expressions of NK-92 cells co-cultured with MDA-MB-231 increased significantly, but this increase was significantly decreased in culture groups with MSCs. IDO expressions increased significantly in co-culture groups with MSCs only. Cytotoxic effects of NK-92 cells were significantly reduced in culture groups with MSCs. However, the suppression effects caused by MSCs improved in the presence of anti-PD-L1 antibodies and in a dose dependent manner. Conclusion: In our findings, we found that MSCs are a highly effective inhibitors, and the IDO enzyme they secrete may play a major role in this. However, the suppressive effects caused by MSCs may be significantly improved by blocking the PD-1/PD-L1 axis. Keywords: Mesenchymal stem cells, NK-92 cells, tumor microenvironment, PD-L1, IDO
Corresponding Author: Alper Tunga Ozdemir