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BLOCKADE OF PD-1/PD-L1 AXIS MAY IMPROVE NK-92 CELL INHIBITION CAUSED BY MESENCHYMAL STEM CELLS

ALPER TUNGA OZDEMİR, CENGİZ KİRMAZ, RABİA BİLGE OZGUL OZDEMİR, MUSTAFA OZTATLİCİ, MEHMET IBRAHİM TUGLU, PİNAR KİLİCARSLAN SONMEZ, KAMİL VURAL, AFİG BERDELİ

Eurasian Journal of Medical Investigation - 2021;5(3):334-340

Medical Biochemistry Laboratory, Merkezefendi State Hospital, Manisa, Turkey Medical Biochemistry Laboratory, Merkezefendi State Hospital, Manisa, Turkey

 

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.