B-1 cells and CCL5/CCR5 axis on tumoral activity of T CD8 lymphocytes

• Grant number: 14/14923-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2014
• End date: September 30, 2016
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Alexandre de Castro Keller
• Grantee: Bruno Camolese Vivanco
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Despite the efforts of many research groups, one issue that still intrigues the scientific community are the mechanisms that control the evolution of neoplastic cells. This is drawing attention to the role of immune cells in the tumor microenvironment, especially innate immunity cells. Among them, macrophages play a controversial role. Some studies show that infiltrating macrophages can control or improve tumor growth. Depending on the situation, these cells are able to inhibit tumor growth by release of oxygen reactive species and cytokines such as TNF-alpha. In other cases, they appear to secrete sufficient levels of growth factors to induce, or at least sustain, a pro-tumor environment. This ambiguity seems to depend on the experimental model and, consequently, on the context which these cells are activated. Our group has been studying this same kind of phenomenon, focusing on B-1 cells, a subpopulation of non-conventional B lymphocytes, which despite the importance they have received in recent years, are still neglected. Previous studies have shown that absence of B-1 cells is associated with mice resistance in the B16F10 murine melanoma model. More recently, we observed that in animals deficient in CCR5, the adoptive transfer of B-1 wild type cells confers resistance to melanoma, a phenomenon associated with the migration of CD8 CCR5-/- to the tumor microenvironment. These data suggest that adoptive transfer of B-1 cells associated with CCR5-blocking would be an alternative therapy for control of melanoma. The aim of this project is to study more deeply the relationship of B-1/CCR5/T CD8 axis in the induction of resistance against melanoma. Since treatment with CCR5 inhibitors is already a therapy against HIV in humans, this experimental design has a great potential in a clinical point of view. (AU)