Immunomodulatory Effects of MDA-MB-231-derived Exosome Mimetic Nanovesicles on CD4+ T Cell Line

Immunomodulatory Effects of MDA-MB-231-derived Exosome Mimetic Nanovesicles on CD4+ T Cell LineB reast cancer is one of the most common types of can- cer in women, and one out of every eight women suffers from this disease.Today, the life expectancy of patients can be extended with the use of biological agents, but tumors that do not express estrogen receptors, progesterone receptors, and HER2, classified as "triple-nega-tive", are resistant to current treatments and have a fatal course. [1,2] romising results are obtained with cancer immunotherapy, a new and effective approach to treating these resistant patients. [3]However, there are several challenges, tumor cells interact intensely with the surrounding tissue, reducing the success rate of both conventional Objectives: The aim of this study is to investigate the immunomodulatory effects of MDA-MB-231 cells or MDA-MB-231-derived exosome-mimetic nanovesicles (NVs) on CD4+ Jurkat cells.Methods: NVs were produced by the breakdown of MDA-MB-231 cells and the characterization of generated NVs were performed by using direct-ELISA and Flow cytometry methods.We co-cultured CD4+ Jurkat cells with MDA-MB-231 cells or MDA-MB-231-derived NVs for 48 h.Subsequently, expressions of pro-inflammatory and anti-inflammatory cytokines, and related transcription factors of CD4+ Jurkat cells were evaluated by qPCR method.Results: Clustering, which is the indicator of activation, was not seen in the CD4+ Jurkat cells co-cultured with MDA-MB-231 cells.However, CD4+ Jurkat cell clusters were observed in the co-culture experiments with all NV concentrations.In addition, it was determined that the expressions of pro-inflammatory cytokines significantly increased while the expressions of anti-inflammatory cytokines was dramatically decreased in the NV-treated groups.On the contrary, opposite results were obtained in CD4+ Jurkat cells co-cultured with MDA-MB-231 cells.Moreover, TNF-α and Gata3 expressions were decreased in all groups.Conclusion: These preliminary findings from in-vitro experiments suggested that NVs could be a potential tool in cancer immunotherapy, but our data need to be supported by more comprehensive studies.