Impact of Aerobic Physical Exercise and the Sympathetic Nervous System on the Modulation of the Tumor Microenvironment and Cancer-Associated Immunosuppression

• Grant number: 25/12002-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2025
• End date: July 31, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Effort
• Principal Investigator: Patricia Chakur Brum
• Grantee: Ricardo Cesar Cintra
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 24/02973-0 - Impact of autonomic nervous system in Cancer: associated mechanisms and effect of exercise training, AP.TEM

Abstract

The influence of the Autonomic Nervous System (ANS) in the tumor microenvironment, especially its role in immunosuppression, is recognized as a crucial aspect for cancer establishment and development. This unfavorable neuro-immune modulation may compromise the efficacy of the anti-tumor immune response and worsen patient prognosis. In this postdoctoral subproject, we will investigate the molecular mechanisms by which aerobic exercise training (AET) can modulate adrenergic signaling in immune cells, aiming to restore their anti-tumor function and reverse immunosuppression in the tumor microenvironment, with a focus on head and neck cancer. Bioinformatics strategies will be employed to identify immune cell populations and molecular targets most affected by beta-adrenergic signaling and AET. Subsequently, the validation of these targets will occur through in vivo experiments, utilizing genetically modified animal models and pharmacological manipulation of adrenergic pathways, and in vitro experiments, in isolated immune cells with targeted receptor modulation. The ultimate goal is to identify new therapeutic strategies that integrate physical exercise into conventional cancer treatment, improving patient prognosis and quality of life. (AU)