Understanding the role of indoleamine-2,3-dioxygenase in the breast tumor microenvironment

• Grant number: 22/16332-1
• Support Opportunities: Regular Research Grants
• Duration: April 01, 2023 - March 31, 2025
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: José Roberto Kfoury Júnior
• Grantee: José Roberto Kfoury Júnior
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ana Claudia Oliveira Carreira Nishiyama ; Cristina de Oliveira Massoco Salles Gomes ; Maria Lucia Zaidan Dagli

Abstract

Nowadays immunotherapy is a popular therapy approach for cancer patients. Although recent progress in cancer immunotherapy has had a significant clinical outcome, not all patients successfully respond to this therapy. Hence, understanding the molecular mechanisms of cancer immunotherapy and anti-tumor immune escape is essential in order to develop more efficient therapies. It is demonstrated that indoleamine-2,3-dioxygenase 1 (IDO1) is involved in various diseases, including inflammatory diseases, cancer, diabetes, and mental disorders. IDO1 is the first rate-limiting step of the kynurenine pathway. The depletion of tryptophan and accumulation of kynurenine in the tumor microenvironment by IDO1 has been explained to cause T cell deactivation, apoptosis, and the induction of immunosuppressive programming. The aim of this project is to evaluate the role of IDO in the molecular mechanisms involved in cancer immunosuppression with a focus on tumor-associated macrophages and T lymphocytes that are critical role players in the immune response to cancer and try to shed light on the role of the IDO1 on the immunosuppression of the breast tumor microenvironment. (AU)