The role of FOLR2+ tissue-resident macrophages during colorectal carcinogenesis.

• Grant number: 25/04637-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Rodrigo Nalio Ramos
• Grantee: Emmanuelle Nascimento Quagliato
• Supervisor: Julie Helft
• Host Institution: Unidade São Paulo. Instituto D'Or de Pesquisa e Ensino (IDOR). Rede D'Or São Luiz (RDSL). São Paulo , SP, Brazil
• Institution abroad: Institut Cochin, France
• Associated to the scholarship: 23/08221-8 - Spatiotemporal evaluation of the transcriptomic profile of FOLR2+ macrophages in Colorectal Cancer, BP.DD

Abstract

Colorectal cancer (CRC) is the second most fatal type of cancer worldwide, and the population affected by this disease is becoming increasingly younger, highlighting the urgent need to understand early diagnosis, initial processes, and disease progression. It is known that various myeloid immune cell types, such as macrophages, which make up the tumor microenvironment (TME), can play critical roles in CRC progression. However, interactions between these subpopulations and tumor cells remain poorly explored.In our recent studies, we reported that FOLR2+ tissue-resident macrophages (FOLR2+ TRM) are present in the stroma of different human tumor types and exhibit molecular profile changes during breast tumor development. FOLR2+ TRM display a metabolic profile in non-tumor tissues but increase the expression of pro-inflammatory/immune-activating genes in the early onset of tumor development, indicating their sensitivity to TME modifications.Therefore, we hypothesize that (1) FOLR2+ TRM sense and respond to early stages of carcinogenesis and (2) consequently play a role in the regulation of anti-tumor immunity. This project aims to decipher the contribution of FOLR2+ TRM in the progression of colorectal cancer and in shaping the immune cell landscape. To this end we will use a newly developed transgenic mouse model (FOLR2-CRE) enabling the selective depletion of FOLR2+ TRM in vivo. This approach will allow us to determine how FOLR2+ TRM contribute to i) tumor progression and ii) to the recruitment and/or activation of lymphocytes during the colon cancer establishment. These findings will improve our understanding of the cellular mechanisms involved in CRC and open new avenues for immunomodulatory therapies targeting macrophages.