The Role of ERK5 Signaling in Regulatory T Cells (Treg) in Colorectal Cancer Progression

• Grant number: 25/15376-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: José Carlos Farias Alves Filho
• Grantee: Gustavo Loria Brunini
• 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

Regulatory T cells (Treg) are a subset of CD4+ T lymphocytes responsible for maintaining immune tolerance. In a tumor context, Tregs contribute to the establishment of an immunosuppressive environment that impairs the recognition and elimination of cancer cells by the immune system. This process contributes to immune evasion and tumor growth, resulting in a worse prognosis for cancer. ERK5 is a kinase of the MAPK family, involved in several intracellular signaling pathways. Studies have shown its influence in modulating the immune system, and in this regard, an unpublished study from our laboratory identified that ERK5 is crucial for the differentiation of Treg lymphocytes. However, its role in the functions performed by Treg cells during cancer progression remain poorly understood. In this project, we propose to investigate the importance of the ERK5 kinase in Treg lymphocytes in the progression of colorectal cancer, one of the most prevalent and lethal types of cancer worldwide. A preclinical model of colorectal cancer will be employed to assess how ERK5 influences the phenotype and function of tumor-infiltrating Tregs and how this modulation impacts tumorigenesis and the composition of the tumor microenvironment. This study may contribute to the development of novel therapeutic strategies targeting the immune system to improve cancer treatment outcomes.