摘要
肿瘤微型环境(TME ) 在肿瘤房间的生长起一个突出的作用。作为 TME 的主要煽动性的部件， M2d 巨噬细胞被 TME 教育以便他们采用支持肿瘤转移和前进的一个抑制免疫力的角色。有 6 月的 Fra-1 形式使活跃之物 protein-1 heterodimers 合伙并且驾驶基因抄写。Fra-1 被认为急速地导致 tumorigenesis 和前进。然而，在 M2d 巨噬细胞的产生的 Fra-1 的功能的角色糟糕迄今为止被理解。这里，我们表明那 4T1 乳房的癌房间与 RAW264.7 巨噬细胞房间 co 有教养，扭曲 RAW264.7 巨噬细胞房间区别进 M2d 巨噬细胞。4T1 房间在 RAW264.7 房间，然后 Fra-1 刺激 Fra-1 的 de novo overexpression 绑在 interleukin 6 (IL-6 ) 在 RAW264.7 房间增加 cytokine IL-6 的生产的倡导者。在 autocrine 的 IL-6 幕塑造扭曲 RAW264.7 巨噬细胞房间区别进 M2d 巨噬细胞。这些调查结果开的新卓见进怎么颠倒 M2d 导致巨噬细胞的有免疫力的忍耐改进 immunotherapeutic 途径的功效。
The tumor microenvironment （TME） plays a prominent role in the growth of tumor cells. As the major inflammatory component of the TME, M2d macrophages are educated by the TME such that they adopt an immunosnppressive role that promotes tumor metastasis and progression. Fra-1 forms activator protein-1 heterodimers with Jun partners and drives gene transcription. Fra-1 is thought to drastically induce tumorigenesis and progression. However, the functional role of Fra-1 in the generation of M2d macrophages is poorly understood to date. Here, we demonstrate that 4T1 mammary carcinoma cells, when co-cultured with RAW264.7 macrophage cells, skew the RAW264.7 macrophage cell differentiation into M2d macrophages. The 4T1 cells stimulate de novo overexpression of Fra-1 in RAW264.7 cells, and then Fra-1 binds to the interleukin 6 （IL-6） promoter to increase the production of the cytokine IL-6 in RAW264.7 cells. IL-6 acts in an autocrine fashion to skew RAW264.7 macrophage cell differentiation into M2d macrophages. These findings open new insights into how to reverse M2d macrophage-induced immune tolerance to improve the efficacy of immunotherapeutic approaches.
