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Spatiotemporal evaluation of the transcriptomic profile of FOLR2+ macrophages in Colorectal Cancer

Grant number: 23/08221-8
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): December 01, 2023
Effective date (End): March 31, 2027
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Rodrigo Nalio Ramos
Grantee:Emmanuelle Nascimento Quagliato
Host Institution: Instituto D'Or de Pesquisa e Ensino (IDOR). Rede D'Or São Luiz (RDSL). São Paulo , SP, Brazil

Abstract

Colorectal cancer (CRC) is the second most fatal type of cancer worldwide, and the population affected by this disease has been getting younger, demonstrating an urgent need for understanding early diagnosis, initial processes, and disease progression. It is known that various myeloid immune cell types, such as macrophages, that compose the tumor microenvironment (TME), can play critical roles in CRC progression. However, the interactions between these subpopulations and tumor cells are still poorly explored. In our recent studies, we reported that tissue-resident FOLR2+ macrophages (FOLR2+ TRM) are present in the stroma of different human tumor types and undergo molecular profile alterations during mammary tumor development. FOLR2+ TRM exhibit a metabolic profile in non-tumor tissues, but they increase the expression of pro-inflammatory/immune-activating genes in medium-sized tumors, thus being sensitive to TME modifications. Therefore, our hypothesis is that FOLR2+ TRM are tissue sentinels critically sensitive to the early processes of carcinogenesis. The present project aims to use a spatial-transcriptomic and temporal in situ approach to decipher 1) how and 2) when the TME could modulate the profile of FOLR2+ TRM during CRC progression in patients and preclinical murine models.This approach will allow us to discover how FOLR2+ TRM act i) in the tumor vascularization process, ii) in tumor progression, and iii) in the chemotaxis and/or activation of lymphocytes during the antitumoral response. Thus, the in-depth characterization of FOLR2+ TRM will reveal critical transcriptional factors and essential modulatory genes that control the development, maintenance, and reprogramming of FOLR2+ TRM in tissues, uncovering potentially predictive molecular factors from the early stages of carcinogenesis. (AU)

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