Transcriptome analysis of CD8 T lymphocytes from patients with Squamous Cell Carcinoma.

• Grant number: 24/10488-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2024
• End date: October 31, 2027
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Ana Paula Campanelli
• Grantee: Renan Lemos da Silva
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
• Associated research grant: 22/15047-1 - Impact of Obesity on CD8+ T cell effector function during tumor development., AP.R

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.