In-vitro Evaluation of Effects of Mesenchymal Stem Cells on TLR3, TLR7/8 and TLR9-activated Natural Killer Cells
Alper Tunga Ozdemir1, Cengiz Kirmaz2, Rabia Bilge Ozgül Ozdemir3, Papatya Degirmenci4, Mustafa Oztatlici5, Mustafa Degirmenci61Department of Medical Biochemistry, Merkezefendi State Hospital, Manisa, Turkey, 2Department of Allergy and Clinical Immunology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey, 3Department of Allergy and Clinical Immunology, Manisa City Hospital, Manisa, Turkey, 4Department of Allergy and Clinical Immunology, Tepecik Training and Research Hospital, Izmir, Turkey, 5Department of Histology and Embryology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey, 6Department of Medical Oncology, Tepecik Training and Research Hospital, Izmir, Turkey,
Objectives: In this study, it was aimed to investigate the immunomodulatory effects of Mesenchymal stem cells (MSCs) on Natural Killer (NK) cells activated by Toll-like receptor (TLR) agonists. Methods: MDA-MB-231, MCF-7 and NK-92 cells were induced with TLR3, TLR7/8 and TLR9 agonists and co-cultured with MSCs. Alterations in IFN-?, TNF-?, Granzyme-b and Perforin expressions were determined by qPCR method, CD69 and CD107a expressions were determined by flow cytometry, and cytotoxicity was determined by MTT-assay. Results: All TLR agonists significantly increased the expressions of the IFN-?, TNF-?, Granzyme-b, Perforin, CD69 and CD107a in-vitro. We determined that the cytokine, cytotoxic molecules, and activation markers of NK-92 cells interacting with breast tumor cells significantly increased by TLR3 and TLR9 agonists. However, suppression rather than activation occurred on the NK-92 cells due to the simultaneous induction of the immunosuppressive effects of MSCs by these agonists. On the other hand, the TLR7/8 agonists provided a low NK-92 induction, however, the inhibitory effects of MSCs were not triggered. Therefore, it provided a more significant activation than TLR3 and TLR9 agonists. Conclusion: Our findings suggested that TLR7/8 agonists may be a better choice to induce antitumor effects of NK cells in a tumor tissue rich in MSCs. Keywords: Toll like receptor agonists, mesenchymal stem cells, natural killer cells, immunomodulation, anti-tumor immunity
Cite This Article
Ozdemir A, Kirmaz C, Ozgül Ozdemir R, Degirmenci P, Oztatlici M, Degirmenci M. In-vitro Evaluation of Effects of Mesenchymal Stem Cells on TLR3, TLR7/8 and TLR9-activated Natural Killer Cells. EJMO. 2021; 5(1): 71-79
Corresponding Author: Alper Tunga Ozdemir