title: Chemokine receptors expression and migration potential of tumor-infiltrating and peripheral-expanded Vgamma9Vdelta2 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U753, from Institut Fédératif de Recherche 54 Villejuif , France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Viey
authors.forename: Claire
authors.initials: C
authors.lastname: Lucas
authors.forename: François
authors.initials: F
authors.lastname: Romagne
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
authors.forename: Anne
authors.initials: A
authors.lastname: Caignard
mesh_terms: D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000235:genetics; D011756:Diphosphates / Q000494:pharmacology; D020869:Gene Expression Profiling; D006801:Humans; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology*; D040081:Protein Array Analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D011756:Diphosphates; D019409:Interleukin-15; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; C521523:T-cell receptor Vdelta2, human; C521522:T-cell receptor Vgamma9, human; C429553:bromohydrin pyrophosphate