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Evaluation of the in vivo treatment with DNA demethylating agents on the development and effector function of CD8T cells

Grant number: 15/25699-2
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): August 01, 2016
Effective date (End): October 31, 2018
Field of knowledge:Biological Sciences - Immunology - Immunogenetics
Principal Investigator:João Gustavo Pessini Amarante Mendes
Grantee:Felipe Campos de Almeida
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):17/03019-5 - Characterization of antigen-specific CD8+ T cells response after in vivo treatment with 5-aza-2'-deoxycytidine., BE.EP.MS


Cancer is a group of diseases that begin when an altered cell starts to divide uncontrollably, invading tissues and impairing the function of a given system of the body. Importantly, cancer is the second leading cause of death worldwide. Therefore, much attention has been given to better understand the molecular mechanisms of tumorigenesis and the immune response to cancer cells, both of which aiming at the development of new ways to treat patients. One of the most promising and novel targets refers to the epigenetic changes observed in cancer cells. The current belief is that DNA demethylating agents act by re-inducing the transcription of tumor suppressor genes otherwise silenced by epigenetic modifications. However, it has been recently demonstrated that DNA demethylation also induces the expression of endogenous dsRNA and the activation of antiviral pathways, a process that was named "viral mimicry". This process contributes to the activation of a long-lasting anti-tumor immune response. However, the impact of in vivo administration of DNA demethylation agents on CD8 T cell expansion, differentiation and function is still poorly understood. Therefore, our project aims to investigate the effect of in vivo administration of 5-Azacytidine on the development and function of the effector CD8 T cells. We will use the well-established system of immunization with recombinant adenoviral vectors, which raises a strong CD8 T cell response, along with ELISPOT (to measure the frequency of antigen-specific CD8 T cell response) and the in vivo cytotoxic assay (to evaluate the in vivo elimination of antigen-specific CD8 T cell targets). (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
YAU, HELEN LOO; BELL, EMMA; ETTAYEBI, ILIAS; DE ALMEIDA, FELIPE CAMPOS; BOUKHALED, GISELLE M.; SHEN, SHU YI; ALLARD, DAVID; MORANCHO, BEATRIZ; MARHON, SAJID A.; ISHAK, CHARLES A.; et al. DNA hypomethylating agents increase activation and cytolytic activity of CD8(+)T cells. MOLECULAR CELL, v. 81, n. 7, p. 1469+, . (17/03019-5, 15/25699-2)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
ALMEIDA, Felipe Campos de. Evaluation of the treatment with DNA demethylating agents on the effector function and antitumor response by the T CD8 lymphocytes. 2018. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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