Investigation of the Epigenetic and Transcriptional landscape of FOLR2+ Macrophages during Colorectal Cancer onset

• Grant number: 25/13029-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2025
• End date: October 31, 2029
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Rodrigo Nalio Ramos
• Grantee: Michel Mouawad de Queiroz
• Host Institution: Unidade São Paulo. Instituto D'Or de Pesquisa e Ensino (IDOR). Rede D'Or São Luiz (RDSL). São Paulo , SP, Brazil
• Associated research grant: 24/04450-5 - FOLR2+ macrophages as immuno-modulators during the carcinogenesis onset: a molecular and spatio-temporal approach, AP.JP

Abstract

Colorectal cancer is one of the most common malignancies and a leading cause of cancer-related mortality worldwide. Its progression is shaped by the tumor microenvironment, a dynamic network of cancer cells, stromal components, and infiltrating immune populations. Tumor-associated macrophages are typically linked to immunosuppression and poor prognosis; however, recent findings from our group indicate that macrophages expressing folate receptor beta are associated with improved clinical outcomes in colorectal cancer. This observation highlights the need to better understand the regulatory mechanisms and functional roles of this subset. These macrophages exhibit context-dependent transcriptional programs, transitioning from metabolic regulation in healthy tissue to gene signatures involved in lymphocyte recruitment and lysosomal function within tumors. The main objective of this project is to characterize the epigenetic profile of these macrophages throughout colorectal cancer progression by integrating spatial transcriptomic and epigenomic data using advanced computational approaches. This will allow investigation of how the tumor microenvironment shapes their phenotype, function, and interactions with cytotoxic T lymphocytes. A key focus will be on how tumor cells influence macrophage reprogramming and how these interactions are spatially organized. The project will also examine associations between genetic mutations in tumor cells and epigenetic remodeling in macrophages. By identifying distinct transcriptional and epigenetic signatures and mapping their spatial context, this research aims to uncover prognostic biomarkers and therapeutic targets, supporting the development of macrophage-centered strategies for colorectal cancer treatment. (AU)