Impact of Obesity on CD8+ T cell effector function during tumor development.

• Grant number: 22/15047-1
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2023
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ana Paula Campanelli
• Grantee: Ana Paula Campanelli
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
• Associated researchers: Karen Angélica Cavassani
• Associated scholarship(s): 25/07294-7 - Analysis of Ferroptosis in Monocytes from Patients with Squamous Cell Carcinoma., BP.IC; 24/10488-5 - Transcriptome analysis of CD8 T lymphocytes from patients with Squamous Cell Carcinoma., BP.DR

Abstract

Evidence shows that obesity is a risk factor for many cancers, but their contribution in human squamous cell carcinoma is unclear. Cholesterol in the tumor microenvironment induces CD8+ T cell functional exhaustion, and inhibition of cholesterol metabolism enhances CD8+ T cell anti-tumor function. Recently, it has been reported increased CD36 expression in tumor infiltrating CD8+ T cells, which was induced by tumor microenvironment cholesterol, and it is associated with tumor progression. Furthermore, CD36 mediated uptake of fatty acids by exhausted CD8+ T cells in tumor microenvironment induced lipid peroxidation and ferroptosis and led to reduced cytokine production and impaired anti-tumor immune response. Understanding the mechanisms that may regulate CD8+ T cell metabolic and its performance in tumor microenvironment could benefit the development of cancer immunotherapy. Given the initial hypothesis that obesity-associated inflammation can promote tumor progression, the present project aims to determine the impact of obesity on CD8+ T cell effector function during tumor development. (AU)