title: B-1 cells promote immunosurveillance against murine melanoma in host absence of CCR5: new perspective in autologous vaccination therapy.
abstract: Autologous vaccination with tumor-primed dendritic cells increases immune response against tumor, which seems to be improved in host absence of CCR5. Because B-1 lymphocytes modulate the activity of different immune cells, we decided to study their influence in the resistance against murine B16F10 melanoma in a CCR5 deprived environment. Adoptive transfer of peritoneal B-1 CCR5(+/+) lymphocytes to CCR5(-/-) animals inhibited the establishment of lung metastasis and melanoma cell growth, in comparison to saline-treated CCR5(-/-) mice. In loco cell analysis demonstrated that the adoptive transfer of B-1 CCR5(+/+) lymphocytes to CCR5 deficient host was associated with a more intense influx of T CD8(+) to tumor site, indicating that the presence of CCR5(+/+) B-1 cells in the tumor environment induces the migration of T CD8 CCR5(-/-) cells to the implantation site. To corroborate this idea, CCR5(-/-) mice were injected with non B-1 peritoneal cells from wild type (WT) mice before B16F10 inoculation. In this regimen, CCR5(-/-) mice were not protected from tumor growth reinforcing the idea that, in host absence of CCR5, B-1 cells are essential to confer tumor resistance. This work indicates that, in the host absence of CCR5, naive B-1 cells may activate CD8T lymphocytes thereby promoting tumor resistance. Our results strongly suggest that autologous vaccination with B-1 lymphocytes in combination with CCR5 antagonists can be an alternative approach to tumor therapy.
authors.affiliation: Universidade Federal de São Paulo, Departamento de Microbiologia, Imunologia e Parasitologia, campus São Paulo, Brazil.
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Vivanco
authors.affiliation: Universidade Federal de São Paulo, Departamento de Microbiologia, Imunologia e Parasitologia, campus São Paulo, Brazil.
authors.forename: Jacqueline D
authors.initials: JD
authors.lastname: Viana
authors.affiliation: Universidade Paulista, campus São Paulo, Brazil.
authors.forename: Elisabeth C
authors.initials: EC
authors.lastname: Perez
authors.affiliation: Universidade Paulista, campus São Paulo, Brazil.
authors.forename: Fabiana T C
authors.initials: FT
authors.lastname: Konno
authors.affiliation: Universidade Federal de São Paulo, Departamento de Microbiologia, Imunologia e Parasitologia, campus São Paulo, Brazil.
authors.forename: Marcia G
authors.initials: MG
authors.lastname: Guereschi
authors.affiliation: Universidade Federal de São Paulo, Departamento de Ciências Biológicas, campus Diadema, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Xander
authors.affiliation: Universidade Federal de São Paulo, Departamento de Microbiologia, Imunologia e Parasitologia, campus São Paulo, Brazil; Universidade Federal de São Paulo, Departamento de Medicina, campus São Paulo, Brazil. Electronic address: ackeller.unifesp@gmail.com.
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Keller
authors.affiliation: Universidade Federal de São Paulo, Departamento de Microbiologia, Imunologia e Parasitologia, campus São Paulo, Brazil; Universidade Federal de São Paulo, Departamento de Ciências Biológicas, campus Diadema, Brazil. Electronic address: jdlopes@unifesp.br.
authors.forename: José D
authors.initials: JD
authors.lastname: Lopes
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D016219:Immunotherapy, Adoptive; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008546:Melanoma, Experimental / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D051379:Mice; D018345:Mice, Knockout; D015166:Monitoring, Immunologic; D019713:Receptors, CCR5 / Q000172:deficiency* / Q000235:genetics
chemical_list: D019496:Cancer Vaccines; D019713:Receptors, CCR5
keywords: Autologous vaccination; B-1 lymphocytes; B16F10 melanoma; CCR5; Tumor