title: Maximal T cell-mediated antitumor responses rely upon CCR5 expression in both CD4(+) and CD8(+) T cells.
abstract: Immune responses against cancer rely upon leukocyte trafficking patterns that are coordinated by chemokines. CCR5, the receptor for chemotactic chemokines MIP1alpha, MIP1beta, and RANTES (CCL3, CCL4, CCL5), exerts major regulatory effects on CD4(+)- and CD8(+) T cell-mediated immunity. Although CCR5 and its ligands participate in the response to various pathogens, its relevance to tumoral immune control has been debated. Here, we report that CCR5 has a specific, ligand-dependent role in optimizing antitumor responses. In adoptive transfer studies, efficient tumor rejection required CCR5 expression by both CD4(+) and CD8(+) T cells. CCR5 activation in CD4(+) cells resulted in CD40L upregulation, leading to full maturation of antigen-presenting cells and enhanced CD8(+) T-cell crosspriming and tumor infiltration. CCR5 reduced chemical-induced fibrosarcoma incidence and growth, but did not affect the onset or progression of spontaneous breast cancers in tolerogenic Tg(MMTV-neu) mice. However, CCR5 was required for TLR9-mediated reactivation of antineu responses in these mice. Our results indicate that CCR5 boosts T-cell responses to tumors by modulating helper-dependent CD8(+) T-cell activation.
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Madrid, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: González-Martín
authors.forename: Lucio
authors.initials: L
authors.lastname: Gómez
authors.forename: Joseph
authors.initials: J
authors.lastname: Lustgarten
authors.forename: Emilia
authors.initials: E
authors.lastname: Mira
authors.forename: Santos
authors.initials: S
authors.lastname: Mañes
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D017931:DNA Primers; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D019713:Receptors, CCR5 / Q000276:immunology*
chemical_list: D017931:DNA Primers; D019713:Receptors, CCR5