Participation of mesenchymal stem cells in the regulation of immune response and cancer development

Marta Elena Castro-Manrreza
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Abstract

The relevance of the microenvironment in the initiation, promotion, and progression of cancer has been postulated. Mesenchymal stem cells (MSCs) have been identified as important components of the tumor stroma, which are capable of affecting the development of cancer through various mechanisms. In particular, MSCs immunosuppressive properties play an important role. It has been shown that bone marrow-derived and other healthy tissues-derived MSCs are capable of regulating the immune response by affecting the activation, maturation, proliferation, differentiation, and effector function of cells of the immune system, such as neutrophils, macrophages, dendritic cells, natural killer cells (NK) and T-lymphocytes. Similar mechanisms have been identified in MSCs associated with different types of tumors, where they generate an immunosuppressive microenvironment by decreasing the cytotoxic activity of T-lymphocytes and NK cells, skew macrophage differentiation towards an M2 phenotype, and decrease the secretion of Th1-type cytokines. Also, the cytokines, chemokines, and factors secreted by the transformed cells or other cells from the tumor stroma are capable of modulating the functions of MSCs.

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间充质干细胞参与免疫反应和癌症发展的调节
微环境在癌症的发生、促进和进展中的相关性已经被假设。间充质干细胞(Mesenchymal stem cells, MSCs)被认为是肿瘤基质的重要组成部分,能够通过多种机制影响癌症的发展。特别是,MSCs的免疫抑制特性起着重要的作用。研究表明,骨髓来源和其他健康组织来源的间充质干细胞能够通过影响免疫系统细胞(如中性粒细胞、巨噬细胞、树突状细胞、自然杀伤细胞(NK)和t淋巴细胞)的激活、成熟、增殖、分化和效应功能来调节免疫反应。在与不同类型肿瘤相关的MSCs中也发现了类似的机制,它们通过降低t淋巴细胞和NK细胞的细胞毒性活性,使巨噬细胞向M2表型分化,并减少th1型细胞因子的分泌,从而产生免疫抑制微环境。此外,转化细胞或肿瘤基质中其他细胞分泌的细胞因子、趋化因子和因子能够调节间充质干细胞的功能。
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