新型免疫抑制性细胞亚群（dMSC）的发现和功能研究

发布时间：2018-07-27 18:00

【摘要】： 髓系抑制性细胞(Myeloid suppressor cells, MSC)是具有多方向分化潜能和免疫抑制功能的未成熟髓系细胞群,为了深入分析其细胞亚类,我们对于肿瘤负荷条件下MSC的表型及功能进行了研究,从肿瘤浸润的淋巴细胞中首次发现了一群新的抑制性细胞亚群,此亚群仅存在于肿瘤瘤体内并可以被肿瘤细胞诱导常规意义上的MSCs(conventional MSC, cMSC )分化而来,故将之命名为dMSC (differentiated MSC)。dMSC伴随肿瘤的发展而比例不断增加;dMSC具有体积小,低表达CD11b、Gr-1和分泌IL-6,高分泌TGF-β1、VEGF、NO、PGE2和MIP-1α等特点;肿瘤细胞分泌的IL-6、VEGF和TGF-β1能够诱导cMSC分化形成dMSC; dMSC能够抑制CD4~+ T细胞的增殖反应,诱导初始T细胞失能和诱导CD4+CD25+Foxp3+调节性T细胞形成, NO是dMSC抑制T细胞增殖的主要因素;dMSC通过自分泌的IL-6诱导MMP-9和VEGF产生而促进肿瘤转移。因此dMSC兼具免疫抑制和诱导肿瘤转移的双重功能, IL-6在dMSC分化形成及其促肿瘤转移中发挥重要作用。该研究为肿瘤免疫逃逸和肿瘤转移提出新的机制,同时也为基于阻断IL-6进行肿瘤免疫治疗提供了新的理论依据。
[Abstract]:Myeloid inhibitory cell (Myeloid suppressor cells, MSC) is an immature myeloid cell group with multidirectional differentiation potential and immunosuppressive function. In order to analyze its cell subtypes, we studied the phenotype and function of MSC under tumor loading. For the first time, a new inhibitory cell subgroup was found in the infiltrated lymphocytes, which exists only in the tumor body and can be induced by tumor cells to differentiate into MSCs (conventional MSC, cMSC) in the conventional sense. Therefore, it was named dMSC (differentiated MSC). DMSC with the development of tumor, and the proportion of DMSC was increasing with small volume, low expression of CD11bnGr-1 and secretion of IL-6, high secretion of TGF- 尾 1 VEGFN PGE2 and MIP-1 伪. IL-6VEGF and TGF- 尾 1 secreted by tumor cells could induce the differentiation of cMSC into dMSCs, and dMSC could inhibit the proliferation of CD4T cells. The primary T cell inactivation and CD4 CD25 Foxp3 regulatory T cell formation were induced. No was the main factor of dMSC inhibiting T cell proliferation. DMSC promoted tumor metastasis by inducing MMP-9 and VEGF production by autocrine IL-6. Therefore, dMSC has the dual functions of immunosuppression and tumor metastasis induction. IL-6 plays an important role in the differentiation and metastasis of dMSC. This study provides a new mechanism for tumor immune escape and tumor metastasis, and also provides a new theoretical basis for tumor immunotherapy based on blocking IL-6.
【学位授予单位】：第二军医大学
【学位级别】：博士
【学位授予年份】：2007
【分类号】：R392

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