Analysis of the contribution of FOLR2+ Macrophages in the formation of Tertiary Lymphoid Structures in Colorectal Cancer

• Grant number: 24/14683-7
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: June 01, 2025
• End date: May 31, 2029
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Rodrigo Nalio Ramos
• Grantee: Kianni Hernandez de Freitas
• 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 (CRC) is considered the second most lethal tumor type globally. According to world statistics, CRC has been shown to be increasing among young adults (under 50 years old), affecting both sexes. Despite efforts in early detection of the disease, approximately half of the patients receive the diagnosis at advanced stage, highlighting the significant relevance and urgency of using new parameters capable of better identifying and understanding this tumor type. Recent studies from our group have identified a subpopulation of tissue-resident macrophages expressing folate receptor-2 (TRM FOLR2+) found in various human tissues and associated with a favorable prognosis for some tumor types. We also report that TRM FOLR2+ are found in lymphoid aggregates and tertiary lymphoid structures (TLS) associated to tumors, which are also associated with a better prognosis in CRC. Additionally, TRM FOLR2+ express high levels of chemokines associated with lymphoid aggregate formation, such as CXCL1, CXCL2, CXCL12, CXCL13. Thus, since TRM FOLR2+ are present in the cancer context and TLSs are associated with a favorable prognosis in cancer, our hypothesis is that TRM FOLR2+ may contribute to the formation, support, and/or maturation of TLS, acting as lymphocyte/immune cells recruiters. Therefore, using modern techniques of spatial transcriptomics associated with immunohistochemical, immunofluorescence labeling, and integrative bioinformatics analyses, the present project aims to understand the contribution of TRM FOLR2+ in the formation of TLS in cohorts of CRC. We intend to decipher the spatial and molecular profile of TRM FOLR2+ and lymphocytes present in TLS, seeking biomarkers that may reveal clinical associations and better stratification of CRC patients, guiding future medical practices for cancer diagnosis and treatment.