Reciprocal Functional Modulation of the Activation of T Lymphocytes and Fibroblasts Derived from Human Solid Tumors
Reciprocal Functional Modulation of the Activation of T Lymphocytes and Fibroblasts Derived from Human Solid Tumors
复制标题
DOI：
10.4049/jimmunol.1000896
复制
发表时间：
2010-09-01
影响因子：
4.4
通讯作者：
Bankert, Richard B.
中科院分区：
文献类型：
--
作者：
Barnas, Jennifer L.;Simpson-Abelson, Michelle R.;Bankert, Richard B.
成纤维细胞是大多数人实体瘤中的主要细胞类型。成纤维细胞具有与肿瘤相关T淋巴细胞相互作用并调节其功能的可能性使其成为潜在的治疗靶点。为了解决这个问题，建立了来源于人肺肿瘤的成纤维细胞的原代培养物，并与来源于相同肿瘤的T细胞一起培养。在CD 3/CD 28诱导的T细胞活化后，肿瘤成纤维细胞显着增强肿瘤相关T细胞产生IFN-γ和IL-17 A。这种增强是成纤维细胞剂量依赖性的，并且不需要两种细胞类型之间的直接接触。肿瘤相关的成纤维细胞条件培养基类似地增强了活化T细胞中的IFN-γ和IL-17 A，并且这种增强被针对IL-6的Ab显著降低。来自活化淋巴细胞培养物的条件培养基显着增强肿瘤成纤维细胞产生IL-6。当来自正常供体的活化T细胞与来自同一供体的皮肤成纤维细胞一起培养时，观察到IFN-γ和IL-17 A的类似增强。这些结果表明，成纤维细胞和自体淋巴细胞，无论是来自肿瘤微环境还是来自非恶性组织，都具有相互作用和调节功能的能力。与其他报道相反，成纤维细胞显示出对活化的T淋巴细胞具有免疫刺激作用。成纤维细胞增强已知对肿瘤进展有影响的两种T细胞细胞因子的能力表明成纤维细胞在肿瘤发病机制中发挥重要作用，可以在治疗上加以利用。免疫学杂志，2010，185：2681-2692。
Fibroblasts are a dominant cell type in most human solid tumors. The possibility that fibroblasts have the capacity to interact with and modulate the function of tumor-associated T lymphocytes makes them a potential therapeutic target. To address this question, primary cultures of fibroblasts derived from human lung tumors were established and cultured with T cells derived from the same tumor. The tumor fibroblasts significantly enhance the production of IFN-gamma and IL-17A by the tumor-associated T cells following a CD3/CD28-induced activation of the T cells. This enhancement was fibroblast cell dose-dependent and did not require direct contact between the two cell types. Tumor-associated fibroblast-conditioned media similarly enhanced both IFN-gamma and IL-17A in activated T cells, and this enhancement was significantly reduced by Abs to IL-6. Conditioned media derived from activated lymphocyte cultures significantly enhanced IL-6 production by tumor fibroblasts. A similar enhancement of IFN-gamma and IL-17A was observed when activated T cells from a normal donor were cultivated with skin fibroblasts derived from the same donor. These results establish that fibroblasts and autologous lymphocytes, whether derived from the tumor microenvironment or from nonmalignant tissues, have the capacity to reciprocally interact and modulate function. In contrast to other reports, fibroblasts are shown to have an immunostimulatory effect upon activated T lymphocytes. The ability of fibroblasts to enhance two T cell cytokines known to have an impact upon tumor progression suggests that fibroblasts play an important role in tumor pathogenesis that could be exploited therapeutically. The Journal of Immunology, 2010, 185: 2681-2692.