Conference 2021 Pre-Recorded Video
Mesenchymal stem cells may be an effective suppressor for the antitumor effects of NK cells induced by TLR3, TLR7/8 and TLR9 agonists
Authors and Affiliations
Alper Tunga Özdemir1, Cengiz Kırmaz2, Rabia Bilge Özgül Özdemir3, Papatya Değirmenci4, Mustafa Öztatlıcı5, Mustafa Değirmenci6
1. Merkezefendi State Hospital, Department of Medical Biochemistry, Manisa, Turkey
2. Manisa Celal Bayar University, Medical Faculty, Department of Allergy and Clinical Immunology, Manisa, Turkey
3. Manisa City Hospital, Department of Allergy and Clinical Immunology, Manisa, Turkey
4. Tepecik Training and Research Hospital, Department of Allergy and Clinical Immunology, Izmir, Turkey
5. Manisa Celal Bayar University, Medical Faculty, Department of Histology and Embryology, Manisa, Turkey
6. Tepecik Training and Research Hospital, Department of Medical Oncology, Izmir, Turkey
Mesenchymal stem cells (MSCs) are potent immunomodulatory cells, and these effects are enhanced by Toll-like receptor (TLR) agonists. MSCs in tumor microenvironment may have the potential to suppress TLR-mediated immune activation. In this study, it was aimed to investigate the effects of MSCs on the TLR agonists-induced antitumor immune response.
Breast tumor cell lines (MDA-MB-231 and MCF-7) and NK-92 cells were co-cultured with and without MSCs. The cells were induced with TLR3, TLR7/8 and TLR9 agonists. 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.
TLR agonists significantly increased the expressions of the IFN-γ, TNF-α, Granzyme-b, Perforin, CD69 and CD107a in-vitro. However, the effect of TLR7/8 agonists was significantly lower than that of other agonists. The antitumor effects of TLR3 and TLR9-induced NK-92 cells were significantly suppressed by MSCs, but not in TLR7/8-induced cells. The cytotoxic effect induced by TLR3 agonists in both MDA-MB-231 and MCF-7 cells was significantly suppressed by MSCs.
TLR3 and TLR9 agonists significantly increased the antitumor effects of NK-92 cells on breast tumor cells in-vitro. However, suppression rather than activation occurred in NK-92 cells due to the simultaneous induction of the immunosuppressive effects of MSCs by these antagonists. 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. Consequently, our findings suggest that the use of TLR7/8 agonists may be a better approach to induce antitumor effects of NK cells in a tumor tissue rich in MSCs.