Chemoimmunomodulation induced by combination of low concentration of 5-fluorouracil with DC vaccine against murine colorectal cancer

• Grant number: 12/17824-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): January 06, 2013
• Effective date (End): July 05, 2013
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ramon Kaneno
• Grantee: Marcela Rodrigues de Camargo
• Supervisor: Sherven Sharma
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Research place: University of Maryland, Baltimore County (UMBC), United States
• Associated to the scholarship: 10/06013-9 - In vivo role of dendritic cell vaccines sensitized with mRNA from MC-38 cells pre-treated with antineoplastic agents at minimum effective doses, BP.DR

Abstract

We have observed that treatment of DC with low concentration of some anti-neoplasic agents, is able to upregulate DC functions and phenotype, as well as increase the susceptibility of tumor cells to specific cytotoxic T lymphocytes. Based on this, we analyzed whether the in vivo combination of low-dose chemotherapy and DC vaccine would be able to increase the immune response to the murine colorectal tumor cells MC-38. Then, our preliminary studies have shown that the combination of minimal effective dose of 5-fluorouracil plus tumor-lysate loaded DC, delayed the development of s.c. tumor mass. It has been hypothesized that DC-based vaccine can be hindered by the infiltration of suppressor cells, such as regulatory T (Treg) and myeloid derived suppressor cells (MDSC). We have also observed that tumor RNA, obtained after cell exposition to minimum effective concentration of 5- fluorouracil was efficient to improve the DC sensitization but did not show an expressive in vivo efficiency. Then, our goal is to evaluate whether these combinations are able to prevent the infiltration of suppressor cells into the tumor microenvironment, aiming: a) to evaluate the in vivo association of DC vaccines with minimum effective or ultra low doses of chemotherapeutics drug; b) to analyse if it is associated with the regulation of Treg and MDSC cells on tumor microenvironment. Functional analysis will include the generation of specific T cells and changes on tumor infiltrating effector cells. (AU)