Blockade of PD-1/PD-L1 Axis May Improve NK-92 Cell Inhibition Caused by Mesenchymal Stem Cells
Alper Tunga Ozdemir1, Cengiz Kirmaz2, Rabia Bilge Ozgul Ozdemir3, Mustafa Oztatlici4, Mehmet Ibrahim Tuglu4, Pinar Kilicarslan Sonmez4, Kamil Vural5, Afig Berdeli61Medical Biochemistry Laboratory, Merkezefendi State Hospital, Manisa, Turkey Medical Biochemistry Laboratory, Merkezefendi State Hospital, Manisa, Turkey, 2Department of Allergy and Clinical Immunology, Manisa Celal Bayar University, Faculty of Medicine, Manisa, Turkey, 3Department of Allergy and Clinical Immunology, Manisa City Hospital, Manisa, Turkey, 4Department of Histology and Embryology, Manisa Celal Bayar University, Faculty of Medicine, Manisa, Turkey, 5Department of Pharmacology, Manisa Celal Bayar University, Faculty of Medicine, Manisa, Turkey, 6Department of Molecular Genetics, Ege University, Faculty of Medicine, Izmir, Turkey
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
Cite This Article
Ozdemir A, Kirmaz C, Ozdemir R, Oztatlici M, Tuglu M, Sonmez P, Vural K, Berdeli A. Blockade of PD-1/PD-L1 Axis May Improve NK-92 Cell Inhibition Caused by Mesenchymal Stem Cells. EJMI. 2021; 5(3): 334-340
Corresponding Author: Alper Tunga Ozdemir