title: Immunosuppressive effect of bone marrow-derived mesenchymal stem cells in inflammatory microenvironment favours the growth of B16 melanoma cells.
abstract: Mesenchymal stem cells (MSCs) are studied for their potential clinical use in regenerative medicine, tissue engineering and tumour therapy. However, the therapeutic application of MSCs in tumour therapy still remains limited unless the immunosuppressive role of MSCs for tumour growth in vivo is better understood. In this study, we investigated the mechanism of MSCs favouring tumour escape from immunologic surveillance in inflammatory microenvironment. We first compared the promotive capacity of bone marrow-derived MSCs on B16 melanoma cells growth in vivo, pre-incubated or not with the inflammatory cytokines interferon (IFN)-γ and tumour necrosis factor (TNF)-α. We showed that the development of B16 melanoma cells is faster when co-injected with MSCs pre-incubated with IFN-γ and TNF-α compared with control groups. Moreover, tumour incidence increases obviously in allogeneic recipients when B16 melanoma cells were co-injected with MSCs pre-incubated with IFN-γ and TNF-α. We then demonstrated that the immunosuppressive function of MSCs was elicited by IFN-γ and TNF-α. These cytokine combinations provoke the expression of inducible nitric oxide synthase (iNOS) by MSCs. The impulsive effect of MSCs treated with inflammatory cytokines on B16 melanoma cells in vivo can be reversed by inhibitor or short interfering RNA of iNOS. Our results suggest that the MSCs in tumour inflammatory microenvironment may be elicited of immunosuppressive function, which will help tumour to escape from the immunity surveillance.
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicial University, Shanghai, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Han
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Tian
authors.forename: Gang
authors.initials: G
authors.lastname: Lv
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Guocheng
authors.initials: G
authors.lastname: Jiang
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Chenyang
authors.initials: C
authors.lastname: Wang
authors.forename: Xinxin
authors.initials: X
authors.lastname: Bu
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
authors.forename: Mengchao
authors.initials: M
authors.lastname: Wu
authors.forename: Lixin
authors.initials: L
authors.lastname: Wei
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D019139:Tumor Escape; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II