Polarization of canine macrophages driven by the expression of Indoleamine 2,3-dioxygenase (IDO) in canine melanocytic tumor cells: in vitro study

• Grant number: 24/14489-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: September 30, 2025
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Cristina de Oliveira Massoco Salles Gomes
• Grantee: Amanda Lofrano Porto
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Immunotherapy has been an important target of study in the fight against cancer, both in humans and animals, generating a growing need for understanding the interaction between tumor cells and the immune system. In this context, the project aims to evaluate the effect of Indoleamine 2,3-dioxygenase (IDO) expression in canine melanocytic tumor cells on the polarization of macrophages derived from blood monocytes. IDO is a rate-limiting enzyme in the kynurenine pathway of tryptophan catabolism, and is associated with immunosuppression and tumor evasion of the immune system through different mechanisms that have not yet been completely elucidated. Thus, the study will be an in vitro analysis using different techniques to evaluate the function and differentiation of macrophages co-cultured with melanocytic tumor cells, with and without the addition of IDO inhibitors, to verify whether the macrophage phenotype is altered by expression of the enzyme in tumor cells and the presence of its metabolites. Analysis of IDO expression will be carried out in a cell line from metastatic lymph nodes of canine oral melanoma, and these cells will be cultured with and without the addition of an IDO inhibitor. At the same time, macrophages will be obtained from blood monocytes, which will be cultivated with the tumor cells, that is, through co-cultures of tumor cells and macrophages, with and without the presence of IDO inhibitor in the co-culture medium. The co-cultures will then be used to evaluate the function and differentiation of macrophages through different in vitro assays.