Extracellular vesicles as an evasion mechanism for cervical cancer - effect on monocytes and macrophages

• Grant number: 24/05804-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2024
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ana Paula Lepique
• Grantee: Matheus Gallardo Souza Inoue
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cervical cancer (CCU) is a global health issue, with Brazil ranking among the countries with the highest incidence and prevalence. Persistent infection with high-risk oncogenic human papillomavirus (HPV) is a key factor in these disease development. Viral oncogenes E6 and E7 play essential roles in HPV-mediated carcinogenesis, and their expression is necessary for maintaining the transformed phenotype. The tumor microenvironment (MT) also plays a role in tumor establishment, being a complex and dynamic environment. Cells such as tumor-associated macrophages (MATs) are influenced by the MT and may develop an immunosuppressive and pro-angiogenic phenotype, promoting tumor growth. Among the various factors secreted in the MT, extracellular vesicles (VEs) have been increasingly studied, with clear evidence that they participate in tumor immunomodulation mechanisms. Previous studies have shown that tumor-derived VEs can modify the phenotype and function of monocytes and macrophages, including their potential for antigen presentation and tolerogenic activity on T lymphocytes. This project aims to further investigate how cervical VEs influence monocytes, and consequently macrophages, in order to better understand CCU progression and contribute to the development of new therapeutic and diagnostic approaches for this disease.