Investigation of mitochondrial dynamics on macrophage polarization in the tumor microenvironment

• Grant number: 22/15815-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2022
• End date: November 30, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Pedro Manoel Mendes de Moraes Vieira
• Grantee: Natália Saran Rando Barros
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 20/16030-0 - Immunometabolic adaptation of tissue resident macrophages in health and disease, AP.TEM

Abstract

Macrophages are diverse and plastic cells of the innate immunity and display an spectrum of phenotypic variations. Among them these phenotypes, in the extremes are the inflammatory and resolution/repair profiles. These different profiles have different metabolisms and consequently mitochondria function. In the tumor microenvironment, these extreme profiles can be found and are correlated with tumor growth. Thus, our objective is to investigate how mitochondrial dynamics affects macrophage polarization and if the polarization of resolving macrophages into an inflammatory profile can decrease tumor growth and metastasis. We will use macrophages that do not express (Fis1 and Opa1), which regulate mitochondrial fission and fusion, respectively. Next, we will analyze whether the deletion of mitochondria dynamics componentes in vitro in macrophages (Drp1 and Mfn1/2) will affect tumor cells. Together, we aim to contribute to the search of new therapeutic pathways, since the repolarization of tumor-associated macrophages is a major target in immunotherapies.