Ozdemir A.T.Kirmaz C.Ozdemir R.B.O.Degirmenci P.Oztatlici M.Degirmenci M.2024-07-222024-07-22202125872400http://akademikarsiv.cbu.edu.tr:4000/handle/123456789/13535Objectives: 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 interact-ing 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. © 2021 by Eurasian Journal of Medicine and Oncology.EnglishAll Open Access; Gold Open AccessCD69 antigengamma interferongranzyme Blysosome associated membrane protein 1perforintoll like receptor 3toll like receptor 7toll like receptor 8toll like receptor 9tumor necrosis factorArticlecell activationcell functioncell interactioncoculturecontrolled studyhumanhuman cellhuman tissueimmunomodulationimmunosuppressive treatmentin vitro studyMCF-7 cell lineMDA-MB-231 cell linemesenchymal stem cellnatural killer cellNK-92 cell lineprotein expressionreal time polymerase chain reactiontumor immunityArticle10.14744/ejmo.2021.15684