Effect of acute lymphoblastic leukemia cells- derived exosome on T cell subsets

Abstract

One of the features of leukemia is characterized by suppression of anti-tumor immunity. Current treatments are based on chemotherapy, which in some cases ends in relapse and in some cases in resistance to chemotreatment. In addition, the immune system, which is usually impaired its function against cancer, and especially in the case of acute lymphoblastic leukemia, should be given more attention. Exosomes are normal extracellular vesicles which play an important role in intercellular communication. Tumor-derived exosomes have significant effects on the target cell because of their contents which have been shown to be compatible with parental cells. Tumor-derived exosomes mediate the immunosuppression by suppressing T cell functions and inducing increasing function of regulatory T cells. On the other hand, exosomes derived from tumor cells can facilitate tumor growth and metastasis. Exosomes derived from tumor cells play an essential role in the escape from immune system. In fact, this process is mediated by exosomes, which can express tumor antigens and suppress T cell signaling. However, more information is needed to understand the effects of exosomes on immune cells, exactly. In this study, the effect of exosomes derived from ALL patients on the T cell of the immune system of normal individuals was investigated. Materials and methods: In this study, exosomes were isolated from the plasma of children with acute lymphoblastic leukemia and incubated for 24 hours with T cells isolated from healthy individuals. The effect of leukemic cell-derived exosomes on the expression of cytokines including IL-10, IL-17, IL-23, TGF-B both in terms of gene expression and in terms of protein was examined by ELISA. In addition, the expression of FOXP-3 and RORγT genes was assessed by RT-PCR technique. Finally, to evaluate apoptosis, BAX and BCL2 gene expression was assessed by RT-PCR, number of apoptotic T cells was measured by flow cytometry, and apoptosis signaling pathway was evaluated by caspases 3 and 9. Findings: The expression of IL-17 and IL-23 genes decreased, and the expression of IL-10 and TGF-B genes has increased, which the results were in line with ELISA results. FOXP-3 increased and RORγT decreased. The results related to apoptosis showed that the BAX gene expression increased and BCL2 gene expression decreased compared to the control group. Also, increasing the rate of apoptosis compared to the control group in flow cytometry and clear bands in caspases 3 and 9 all indicate increased apoptosis in the environment containing exosomes. All results, except for TGF-B results, are significant in gene expression and protein count.