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首页> 外文期刊>Journal of immunotherapy >Chemokine receptors expression and migration potential of tumor-infiltrating and peripheral-expanded Vgamma9Vdelta2 T cells from renal cell carcinoma patients.
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Chemokine receptors expression and migration potential of tumor-infiltrating and peripheral-expanded Vgamma9Vdelta2 T cells from renal cell carcinoma patients.

机译:肾细胞癌患者肿瘤浸润和外周扩张的Vgamma9Vdelta2 T细胞的趋化因子受体表达和迁移潜力。

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We previously showed that Vdelta2 T cells infiltrate renal tumors and can be expanded as potent cytotoxic effectors from peripheral blood mononuclear cells of most renal cell carcinoma (RCC) patients, using a structural analog of nonconventional T-cell receptor gamma9delta2 ligand, bromohydrin pyrophosphate, and interleukin-2 (IL-2). In this study, we have further investigated the differentiation status and the migration potential of circulating and tumor-infiltrating Vgamma9Vdelta2 T lymphocytes from RCC patients. The repertoire of tumor-infiltrating and peripheral Vgamma9Vdelta2 T cells from RCC patients was characterized by a dominant CD27- CD45RA- subset. These effector memory Vgamma9Vdelta2 T cells were efficiently expanded using bromohydrin pyrophosphate combined with IL-15, but not IL-2. In addition, peripheral Vgamma9Vdelta2 T cells from RCC patients present a modified chemotactic pattern compared with donors. After ex vivo activation, peripheral expanded Vgamma9Vdelta2 T cells acquire low-migration capacities toward renal cells. Tumor-infiltrating Vgamma9Vdelta2 T cells migrated with higher efficiency toward primary renal tumor cells. The traffic toward tumor cells required the CXCL12/CXCR4 interaction. Altogether, these results outline that those Vgamma9Vdelta2 effectors exhibit differential migration capacities according to their localization, their differentiation status, and the tumor microenvironment parameters that may influence their use in immunotherapy.
机译:我们先前显示,使用非常规T细胞受体gamma9delta2配体,溴化氢焦磷酸和白介素2(IL-2)。在这项研究中,我们进一步研究了来自RCC患者的循环和浸润性Vgamma9Vdelta2 T淋巴细胞的分化状态和迁移潜力。来自RCC患者的肿瘤浸润和外周Vgamma9Vdelta2 T细胞库的特征是显性的CD27-CD45RA-亚群。这些效应记忆Vgamma9Vdelta2 T细胞使用溴化氢焦磷酸与IL-15,但不是IL-2联合有效地扩增。此外,与供体相比,RCC患者的外周血Vgamma9Vdelta2 T细胞呈现出改良的趋化模式。在离体激活后,外周扩张的Vgamma9Vdelta2 T细胞获得了向肾细胞的低迁移能力。肿瘤浸润性Vgamma9Vdelta2 T细胞向原发性肾肿瘤细胞迁移的效率更高。朝向肿瘤细胞的运输需要CXCL12 / CXCR4相互作用。总而言之,这些结果概述了那些Vgamma9Vdelta2效应物根据其定位,分化状态以及可能影响其在免疫疗法中的应用的肿瘤微环境参数而显示出不同的迁移能力。

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