In-vitro Evaluation of Effects of Mesenchymal Stem Cells on TLR3, TLR7/8 and TLR9-activated Natural Killer Cells
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-γ, TNF-α, 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-γ, TNF-α, 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.
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