The effects of mesenchymal stem cells on the IDO, HLA-G and PD-L1 expression of breast tumor cells MDA-MB-231 and MCF-7

Abstract

Aim: Mesenchymal stem cells (MSCs) are strong immunomodulatory cells and a component of the tumor microenvironment. In this study, we aimed to investigate the effects of MSCs derived from adipose tissue on the expressions of immune evasive molecules indoleamine 2,3-dioxygenase (IDO), human leukocyte antigen G (HLA-G) and programmed death-ligand 1 (PD-L1) of breast tumor cell lines MDA-MB-231 and MCF-7. Methods: For this purpose, MSCs, MDA-MB-231 and MCF-7 cells were cultured with increased doses of interferon gamma (IFN-g). In another plate, tumor cells were cultured in transwell inserts using the same IFN-g stimulation to evaluate the effect of MSCs. At the end of the culture period, the HLA-G and PD-L1 expression was detected by flow cytometry, and IDO expression by the Luminex method. Results: We found that in low-dose IFN-g stimulation (10 ng/mL), MSCs led to a significant increase in the HLA-G and PD-L1 expression of MCF-7 cells. On the contrary, at a high dose of IFN-g (50 ng/mL), their expression significantly decreased in both tumor cells. In addition, we observed that the IDO expression of MDA-MB-231 cells was significantly increased in the presence of MSCs, but MCF-7 cells were not affected. Conclusion: In conclusion, for MDA-MB-231 cells, MSCs may play a protective role because they reduce the expression of HLA-G and PD-L1 that are involved in the suppression of cytotoxic cells and exhaustion of T cells. On the other hand, MSCs may be an important source of high IDO levels, and therefore may negatively affect the antitumor immune response. However, our data should be supported by further studies.

The Effects of Preconditioning with IFN-γ, IL-4 and IL-10 on Costimulatory Ligand Expressions of Mesenchymal Stem Cells

“…highly expressed by MSCs [4][5][6]. Therefore, they are used experimentally in the treatment of many autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and Crohn's disease.…”

“…IFN-γ is also effective on the surface molecules of MSCs. It has been reported that immune regulatory surface molecule expressions, such as PD-L1, HLA-G, vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), were increased with IFN-γ stimulation [6,10,11]. In addition to IFN-γ, tumor necrosis factor alpha (TNF-α), IL-6, and IL-17, may be used.…”