Blockade of PD-1/PD-L1 Axis May Improve NK-92 Cell Inhibition Caused by Mesenchymal Stem Cells

• Published in: Eurasian journal of medical investigation 2021, Vol.5 (3), p.334
• Main Author: Ozdemir, Alper Tunga
• Format: Article
• Language: eng ; tur
• Subjects: Antibodies; Cytotoxicity; Enzymes; Ligands; Stem cells
• ISSN: 2602-3164; 2602-3164
• DOI: 10.14744/ejmi.2021.49785

[LANGUAGE= "English"] Objectives: In this study, it was aimed to investigate how the effects of Mesenchymal stem cells (MSCs) on the anti?tumor 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 anti?PD-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. How?ever, the suppression effects caused by MSCs improved in the presence of anti-PD-L1 antibodies and in a dose depen?dent 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.