In-vitro Evaluation of Effects of Mesenchymal Stem Cells onTLR3, TLR7/8 and TLR9-activated Natural Killer Cells
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Date
2021
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Abstract
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-culturedwith MSCs. Alterations in IFN-γ, TNF-α, Granzyme-b and Perforin expressions were determined by qPCR method, CD69and 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-γ, TNF-α, Granzyme-b, Perforin, CD69 andCD107a in-vitro. We determined that the cytokine, cytotoxic molecules, and activation markers of NK-92 cells interact ing with breast tumor cells significantly increased by TLR3 and TLR9 agonists. However, suppression rather than activa tion occurred on the NK-92 cells due to the simultaneous induction of the immunosuppressive effects of MSCs by theseagonists. On the other hand, the TLR7/8 agonists provided a low NK-92 induction, however, the inhibitory effects ofMSCs 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 cellsin a tumor tissue rich in MSCs.