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Role of regulatory T cells in the development of Colorectal Cancer in mices post - Sepsis

Grant number: 14/03650-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2014
Effective date (End): July 31, 2018
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal researcher:Fernando de Queiroz Cunha
Grantee:Letícia Almeida Do Nascimento
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Sepsis can be defined as an exaggerated inflammatory response caused by infection with high incidence (20-30 million people / year) and mortality (30.8 % ) . Recently, it was shown that survivors patients of sepsis are prone to infection by a second normally non-pathogenic causes. During this period an anti - inflammatory response with accumulation of regulatory T cells (Treg) is observed. Preliminary data from our group showed that murine melanoma tumor progression during this period, associated with profound alterations in the tumor microenvironment. This project aims to investigate if the post- sepsis state favors the occurrence of colorectal cancer (CRC ) , and this phenomenon may be mediated by Tregs . To assess tumor initiation in the post - sepsis, animals should be subjected to cecal ligation and puncture ( CLP ) to induce sepsis procedure and naïve animals as control . Survivors will be treated with DTA - 1 antibodies (to inhibit the regulatory function of Tregs). For induction of CCR, animals should be subjected to treatment with azoxymethane ( AOM ) ( ip ) , followed by weekly cycles of dextran sulfate sodium ( DSS ) 2.5 % diluted in drinking water . Colonoscopies are performed weekly to assess colitis and tumor growth. The animals will be sacrificed after 25, 45 or 65 days for quantification of Treg in the tumor healthy colon, spleen and mesenteric lymph nodes by flow cytometry.