Effects of caloric restriction, time-restricted feeding, and exercise in B lymphocytes' anti-tumor responses

• Grant number: 23/01164-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: October 02, 2023
• End date: October 01, 2024
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Luísa Menezes Silva
• Supervisor: Nicholas Collins
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Weill Cornell Medical College, United States
• Associated to the scholarship: 21/03192-4 - Metabolism and B lymphocytes: effects of caloric restriction on the mitochondrial dynamics of B-1 cells, BP.DR

Abstract

Dietary restriction and exercise are known to promote numerous physiological benefits. These include extending longevity, improving metabolic profiles and tissue regeneration, as well as reducing neurodegeneration, bone loss, cardiovascular disease, and the incidence of cancer. Emerging evidence indicates that these interventions can also optimize immune responses. This can be mediated directly by influencing cell metabolism and indirectly by regulating the composition and function of the microbiota. Recently, it was demonstrated that caloric restriction could enhance memory T cell function to promote host protection against pathogens and tumors. In addition, preliminary data obtained during this current project indicate that caloric restriction improves B cells' humoral functions in a T-independent antigenic challenge. Of late, it was proposed that B cell responses could also play a part in the tumor microenvironment and that IL-10-producing B cell populations promote the ability of tumors to evade the immune system. In this project, we aim to evaluate the impact of dietary restriction, combined with exercise protocols, on B lymphocyte function in the setting of antitumor responses. By using flow-cytometry-based metabolic analysis (SCENITH), tissue clearing and immunofluorescence, and single-cell analysis of the B lymphocyte subpopulations, we aim to understand how diet and exercise affect the ability of B cells to regulate cancer progression in a melanoma model. We hypothesize that restricting dietary intake in combination with physical activity will support optimal host fitness by promoting optimal antitumoral responses. (AU)