• Open Access

Immunosuppressive effect of bone marrow-derived mesenchymal stem cells in inflammatory microenvironment favours the growth of B16 melanoma cells

Authors

  • Zhipeng Han,

    1. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicial University, Shanghai, China
    2. Stem Cell and Medicine Postgraduate Innovation Experiment Center, The Second Military Medical University, Shanghai, China
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    • These authors contributed equally to this work.

  • Zhiqiang Tian,

    1. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicial University, Shanghai, China
    2. Department of General Surgery, 101th Hospital of Chinese People’s Liberation Army, Wuxi, Jiangsu, China
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    • These authors contributed equally to this work.

  • Gang Lv,

    1. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicial University, Shanghai, China
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  • Li Zhang,

    1. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicial University, Shanghai, China
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  • Guocheng Jiang,

    1. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicial University, Shanghai, China
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  • Kai Sun,

    1. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicial University, Shanghai, China
    2. Stem Cell and Medicine Postgraduate Innovation Experiment Center, The Second Military Medical University, Shanghai, China
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  • Chenyang Wang,

    1. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicial University, Shanghai, China
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  • Xinxin Bu,

    1. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicial University, Shanghai, China
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  • Rong Li,

    1. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicial University, Shanghai, China
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  • Yufang Shi,

    1. Institute of Health Sciences and Shanghai Institute of Immunology, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Mengchao Wu,

    1. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicial University, Shanghai, China
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  • Lixin Wei

    Corresponding author
    1. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicial University, Shanghai, China
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Lixin WEI, Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicial University, 225 Changhai Road, Shanghai 200438, China. Tel.: +86–21-81875331 Fax: +86–21-35030398 E-mail: lixinwei@smmu.edu.cn

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.

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