Dynamics of regulatory T lymphocytes in immunosurveillance and antitumor response

• Grant number: 25/11434-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2025
• End date: June 30, 2027
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: José Carlos Farias Alves Filho
• Grantee: Bruno Marcel Silva de Melo
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Different regulatory mechanisms of the immune system are used to ensure host homeostasis. Some of these mechanisms are controlled by regulatory T lymphocytes (Treg), which are considered the main cells that mediate peripheral tolerance. In fact, mice or individuals with mutations in the FOXP3 gene develop an autoimmune lymphoproliferative syndrome that causes organ damage and dysfunction. While Treg lymphocytes protect the host from an exacerbated inflammatory response and autoimmunity, attenuated immune responses mediated by these cells, in conditions of infection and tumor, are unfavorable to the host. Additional studies demonstrate that the depletion of Treg lymphocytes in tumor models or the use of checkpoint inhibitors as a pharmacological tool in cancer patients, improves the antitumor immune response. However, the mechanisms by which Treg cells control this immune response in tumorigenesis remain poorly understood. In this sense, our project aims to investigate the mechanisms of immune control mediated by Treg cells in the tumor microenvironment, specifically in metastatic colorectal cancer (mCRC). CRC is one of the most common cancers worldwide, with an estimated two million new cases and almost one million deaths per year. Although the prognosis of patients with CRC has slowly improved in the last decades, mCRC is still associated with a dramatic survival of less than 15% of these patients. The liver is the most common site for CRC metastases, and up to 75% of patients with mCRC present liver metastases (10). Although metastatic disease is the main cause of death in CRC, its molecular basis remains poorly defined, which hinders the development of therapeutic strategies. Understanding the dynamics and profile of Treg lymphocytes in this microenvironment may help in the development of new pharmacological disciplines to improve the antitumor immune response and increase the survival rate of these patients. (AU)