Chemokine receptors expression and migration potential of tumor-infiltrating and peripheral-expanded Vγ9Vδ2 T cells from renal cell carcinoma patients

We previously showed that V delta 2 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 gamma 9 delta 2 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 V gamma 9V delta 2 T lymphocytes from RCC patients. The repertoire of tumor-infiltrating and peripheral V gamma 9V delta 2 T cells from RCC patients was characterized by a dominant CD27(-) CD45RA(-) subset. These effector memory V gamma 9V delta 2 T cells were efficiently expanded using bromohydrin pyrophosphate combined with IL-15, but not IL-2. In addition, peripheral V gamma 9V delta 2 T cells from RCC patients present a modified chemotactic pattern compared with donors. After ex vivo activation, peripheral expanded V gamma 9V delta 2 T cells acquire low-migration capacities toward renal cells. Tumor-infiltrating V gamma 9V delta 2 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 V gamma 9V delta 2 effectors exhibit differential migration capacities according to their localization, their differentiation status, and the tumor microenvironment parameters that may influence their use in immunotherapy.