T lymphocyte recruitment into renal cell carcinoma tissue: a role for chemokine receptors CXCR3, CXCR6, CCR5, and CCR6

淋巴细胞募集至肾细胞癌组织:趋化因子受体 CXCR3、CXCR6、CCR5 和 CCR6 的作用

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作者:Kimberley A Oldham, Greg Parsonage, Rupesh I Bhatt, D Michael A Wallace, Nayneeta Deshmukh, Shalini Chaudhri, David H Adams, Steven P Lee

Background

Evidence suggests that some patients with renal cell carcinoma (RCC) respond to immunomodulatory therapies that activate T lymphocytes. A prerequisite for effective T cell therapy is efficient targeting of effector T cells to the tumour site, yet the molecular basis of T cell recruitment to RCC is unknown. Furthermore, some T cells that naturally infiltrate this cancer are regulatory T cells (Tregs) that may suppress antitumour immune responses.

Conclusions

Our data support a role for CCR5, CXCR3, and CXCR6 in the selective recruitment of T cells into RCC tissue and, together with CCR6, in the recruitment of Tregs.

Objective

Determine the mechanisms of effector and regulatory T cell recruitment to RCC to allow targeted therapy that promotes local anti-tumour immunity. Design, setting, and participants: Tumour-infiltrating and peripheral blood T cells were collected from 70 patients undergoing nephrectomy for RCC. Measurements: T cells were analysed by multicolour flow cytometry for expression of 19 chemokine receptors and 7 adhesion molecules. Receptors that were expressed at higher levels on tumour-infiltrating lymphocytes (TILs) compared with matched peripheral blood lymphocytes (PBLs) were analysed further for their ability to mediate migration responses in TILs and for expression of corresponding ligands in tumour tissue.

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