Abstract A087: The immunosuppressive property of mesenchymal stem cell in an apoptotic tumor microenvironment

Abstract

Mesenchymal stem cells (MSCs) are a heterogeneous population of multipotenT-cells and are capable of differentiating into certain cell types. They can be found within tumor core and constitute part of the tumor microenvironment. Their role in tumor progression remains contradictory with both sides arguing pro- and anti-tumor function. In regarding to the pro-tumor effect, MSCs have shown to have immunoregulatory properties—suppressing T lymphocytes, B lymphocytes and dendritic cells, thereby helping tumor cells to escape from the immune surveillance. However there are some studies that showed certain microenvironment and stimulation can drive MSC into a proinflammatory phenotype. During cancer therapy, large amount of apoptotic cells are released to the tumor microenvironment. The aim of this study is to investigate how an apoptotic microenvironment can affect the function of MSC on naive T-cells. Apoptotic cells (ACs) were derived from the neuroblastoma cell line SK-N-LP treated with cisplatin for 24 hr; they were then co-cultured with the immortalised human MSC cell line (hTMSC). Naive T-cells were isolated from peripheral blood mononuclear cells of healthy donors and further co-cultured with either hTMSC alone or AC-treated hTMSC (hTMSC-AC) for 5 days. Cell proliferation and phenotype were analyzed by flow cytometry. We demonstrated that hTMSCs have the ability to phagocytose AC. After engulfment, the hTMSC-AC were able to increase T-cell proliferation compared to those co-cultured with untreated hTMSC. The T-cells co-cultured with hTMSC-AC also showed a decrease in CD45RA expression, suggesting an increase in T-cell activation. Moreover, these T-cells had a higher expression level of interferon-gamma (IFN-γ) and a lower expression of FoxP3, indicating a shift towards proinflammatory effector T-cells and a reduction of regulatory T-cells. Consistent with other literature, hTMSC has the ability to supress T-cells’ activation and proliferation. However in the presence of AC, hTMSC immunosuppressive property was impeded, thereby heightening the immune response. Therefore the microenvironment can play a major factor in determining the role of MSC on tumor. Further investigation of the interaction of MSC with immune cells in an apoptotic tumor microenvironment can lead to a potential immunotherapy for neuroblastoma. Citation Format: Anita K.Y. Li, Carmen J.M. Cao, Godfrey C.F. Chan. The immunosuppressive property of mesenchymal stem cell in an apoptotic tumor microenvironment [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A087.