Chemokine Receptors Expression and Migration Potential of Tumor-infiltrating and Peripheral-expanded Vγ9Vδ2 T Cells From Renal Cell Carcinoma Patients

Abstract

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.