Blockade of PD-1/PD-L1 Axis May Improve NK-92 CellInhibition Caused by Mesenchymal Stem Cells
Date
2021Author
Rabia Bilge ÖZGÜL ÖZDEMİR
Alper Tunga ÖZDEMİR
Afig BERDELİ
Cengiz KIRMAZ
Kamil VURAL
Mehmet İbrahim TUĞLU
Mustafa ÖZTATLICI
Pınar Kilicarslan SÖNMEZ
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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-L1antibody. IFN-γ, TNF-α, IL-10 and IDO levels of medium supernatants were determined by ELISA. CCK-8 kit was used toevaluate cytotoxic activity. Results: IFN-γ and TNF-α expressions of NK-92 cells co-cultured with MDA-MB-231 increased significantly, but thisincrease was significantly decreased in culture groups with MSCs. IDO expressions increased significantly in co-culturegroups 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 mayplay a major role in this. However, the suppressive effects caused by MSCs may be significantly improved by blockingthe PD-1/PD-L1 axis.
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