B-1 cells promote immunosurveillance against murine melanoma in host absence of CCR5: New perspective in autologous vaccination therapy

• Published in: Immunobiology (1979) Vol. 219; no. 11; pp. 845 - 849
• Main Authors: Vivanco, Bruno C, Viana, Jacqueline D, Perez, Elisabeth C, Konno, Fabiana T.C, Guereschi, Marcia G, Xander, Patricia, Keller, Alexandre C, Lopes, José D
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier GmbH 01.11.2014
• Subjects: Adoptive Transfer; Advanced Basic Science; Allergy and Immunology; Animals; Autologous vaccination; B-1 lymphocytes; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; B16F10 melanoma; Cancer Vaccines - immunology; CCR5; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Cell Movement - genetics; Immunotherapy, Adoptive; Lymphocytes, Tumor-Infiltrating - immunology; Male; Melanoma, Experimental - genetics; Melanoma, Experimental - immunology; Melanoma, Experimental - mortality; Melanoma, Experimental - pathology; Melanoma, Experimental - therapy; Mice; Mice, Knockout; Monitoring, Immunologic; Receptors, CCR5 - deficiency; Receptors, CCR5 - genetics; Tumor; TAM; Autologous vaccination; extracellular-signal-regulated kinase; B16F10 melanoma; RANTES; tumor-associated macrophage; EDTA; MAPK; NF-κB; dendritic cells; B-1 lymphocytes; CCL5; Chemokine (C-C motif) ligand 5; mitogen-activated protein; regulated on activation, normal T cell expressed and secreted; Tumor; C-C chemokine receptor type 5; wild type; CCR5; WT; nuclear factor kappa-light-chain-enhancer of activated B cells; DC; ethylenediamine tetraacetic acid; ERK
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2014.07.013

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.