Effect of DNA Methyltransferase inhibitors (DNMTi) on CD8 T cell differentiation and evaluation of the combined effect of DNMTi and immunotherapy on in vivo antitumor response

• Grant number: 18/12691-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2018
• End date: November 30, 2021
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: João Gustavo Pessini Amarante Mendes
• Grantee: Tandressa Souza Berguetti
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cancer can be described as a collection of related diseases where accumulation of mutations causes exaggerated cell proliferation and/or resistance to cell death. The relationship between cancer cells and the immune system is dynamic. Immune cells may recognize and kill tumor cells in a process known as immunosurveillance. Some tumor cells present tumor-associated antigens that can be recognized by the immune system. However, it has been reported that the expression of these antigens is predominantly under the control of epigenetic regulation. For this reason, demethylation agents have been considered strategic tools in Cancer treatment. These agents widely alter gene expression and potentially hinder tumor cell evasion of the immune system. Interestingly, activation and differentiation of CD8 T lymphocytes, one of the important mechanisms of anti-tumor immune responses, involves changes in DNA methylation profile. The aims of this project are to understand the effect of DNA demethylating agents on CD8 T subset differentiation and effector function, and how this impact on combined anti-tumor chemo/immune therapies. (AU)