Role of acute and chronic aerobic exercise on anti-tumor and anti-inflammatory response of dendritic cells and macrophages

• Grant number: 24/05048-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2025
• End date: February 29, 2028
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: José Cesar Rosa Neto
• Grantee: Caíque de Figueiredo
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Monocytes are circulating immune cells that can migrate to peripheral tissues and differentiate into macrophages and dendritic cells. The final phenotype of these differentiated cells is influenced by the tissue microenvironment, particularly in tumor settings, where it can bias differentiation towards pro-tumoral phenotypes. Different subpopulations of monocytes exhibit varying responses to differentiation stimuli, with classical monocytes showing more pro-tumoral and anti-inflammatory phenotypes compared to non-classical monocytes. Interestingly, a single session of aerobic exercise alters the transcriptional profile, enhances phagocytic and microbicidal capacity, and transiently reduces anti-inflammatory pathway activation in monocytes, potentially priming a robust response to exercise-induced stress. In this proposed study involving individuals with or without breast cancer undergoing an acute aerobic exercise session before and after aerobic training, monocyte subpopulations will be differentiated into macrophages and dendritic cells. Various experiments and analyses will be conducted to elucidate how exercise impacts monocyte subpopulations and influences the anti-tumoral and inflammatory profiles of dendritic cells and macrophages. The hypothesis posits that aerobic exercise (acute session and chronic training) will prepare monocytes, especially non-classical subpopulation, to differentiate into cells with enhanced anti-tumoral and inflammatory capabilities. The proposed mechanisms involve differential cellular-level cytokine action and AMPK activation among monocyte subpopulations post-exercise.