Interleukin-1α induces immunosuppression by mesenchymal stem cells promoting the growth of prostate cancer cells

Abstract

Mesenchymal stem cells (MSCs) are generally used in tissue engineering, regenerative medicine and therapy for immune disorder disease. MSCs are also employed as drug carriers for tumor therapy due to their ability to migrate to tumor tissue. However, due to the immunosuppressive function of MSCs, the application of MSCs in prostate cancer therapy remains limited. In this study, we investigated the underlying mechanism by which MSCs enable prostate cancer cells to escape from immune surveillance in the inflammatory microenvironment. Firstly, we demonstrated that compared with the control groups, MSCs pretreated with IL-1α effectively promoted the growth of the mouse prostate cancer cell line RM-1 invivo. Furthermore, when RM-1 prostate cancer cells were co-injected with MSCs pretreated with IL-1α, tumor incidence significantly increased in allogeneic recipients. In addition, we investigated the mechanism through which MSCs promote the ability of RM-1 cells to escape from immune injury. The results revealed that IL-1α led to the upregulation of TGF-β in MSCs. The inflammatory cytokine-induced promotive effect of MSCs on RM-1 cells in vivo was inhibited by TGF-β siRNA. The results of our study suggest that inflammatory cytokines induce the immunosuppressive function of MSCs which enables prostate cancer cells to escape from immune injury.