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Metabolic impact of metformin in the anti-tumor T cell response

Grant number: 15/21513-1
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): March 07, 2016
Effective date (End): February 13, 2017
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Niels Olsen Saraiva Câmara
Grantee:Felipe Valença Pereira
Supervisor abroad: Susan Kaech
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Yale School of Medicine (YSM), United States  
Associated to the scholarship:13/10318-8 - Immunobiological actions of adipokines in experimental murine model of melanoma., BP.PD

Abstract

The tumor microenvironment is notoriously immunosuppressive and the holy grail of tumor immunology is to devise methods to restimulate the immune cells to reject tumor cells and halt tumor progression and death. Through the study of genetically engineered models of melanoma and lung cancer in mice, we are characterizing the changes that occur in the immune cells, particularly the tumor associated macrophages (TAMs) and T cells, during chemo- and immuno-therapies. This work is necessary to understand the action of anti-cancer drugs and identify targeted therapies that work best in conjunction with immunotherapies, such as PD-1 or CTLA-4 blockade. Metformin is one of the most prescribed drugs for the treatment of type 2 diabetes (T2D). Recently, several studies has been demonstrated an anticancer effect of metformin. Epidemiological data showed that diabetic patients treated with metformin have a decrease in cancer incidence. Metformin is an agonist of AMPK, a metabolic sensor pathway involved in different processes of cellular energy homeostasis. The anticancer mechanisms attributed to metformin include a direct activity in cancer cell metabolism, regulation of cell cycle control and cell death induction. Here, we will investigate immunometabolic mechanisms that metformin could act directly on melanoma cells as well as in T cell present on tumor microenvironment. (AU)

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