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The role of microbiota in the development of Th9 cells-mediated antitumor activity

Grant number: 15/13817-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2015
Effective date (End): January 31, 2017
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Niels Olsen Saraiva Câmara
Grantee:Rafael Ribeiro Almeida
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The microbiota has a crucial role in the development of gut-associated lymphoid tissue, polarization of immune responses and prevention against pathogen colonization. The secretion of cytokines (IL-1b, IL-6 and IL-18) in response to commensal bacteria and some microbiota metabolites (ATP and short-chain fatty acids) contribute to gut homeostasis and generation of lymphoid cells, such as IL-17-producing gd T lymphocytes, Th17 cells, regulatory T and B cells. It has been shown that gut microbiota is fundamental for generating antitumor immune responses. However, the mechanisms are poorly understood. The Th9 cells develop in the presence of IL-4 and TGF-b and show increased antitumor activity when polarized in the presence of IL-1b, cytokines that are produced in the gut microenvironment. Thus, we hypothesized that the microbiota participates in the development of Th9 cells-mediated antitumor activity. We intend to evaluate the impact of the microbiota and its metabolites on the frequency/function of Th9 cells in the lamina propria, mesenteric lymphnodes, spleen and infiltrated in the melanoma tumor. We seek to evaluate the impact of Th9 cells adoptive transfer on tumor growth in microbiota-depleted mice. We also aim to determine the role of MYD88 signaling in both intestinal villi and dendritic cells on the development of microbiota-dependent Th9 cells antitumor activity. We believe that the study of mechanisms involved in the generation of microbiota-dependent antitumor immune responses is necessary, especially for the design of new therapeutic anticancer strategies.

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)
ALMEIDA, RAFAEL RIBEIRO; VIEIRA, RAQUEL DE SOUZA; CASTOLDI, ANGELA; TERRA, FERNANDA FERNANDES; MELO, AMANDA CAMPELO L.; CAMPOS CANESSO, MARIA CECILIA; LEMOS, LUISA; CIPELLI, MARCELLA; RANA, NISHA; HIYANE, MEIRE IOSHIE; PEARCE, ERIKA L.; MARTINS, FLAVIANO DOS SANTOS; CAETANO DE FARIA, ANA MARIA; SARAIVA CAMARA, NIELS OLSEN. Host dysbiosis negatively impacts IL-9-producing T-cell differentiation and antitumour immunity. BRITISH JOURNAL OF CANCER, JUN 2020. Web of Science Citations: 0.
VIEIRA, RAQUEL DE SOUZA; CASTOLDI, ANGELA; BASSO, PAULO JOSE; HIYANE, MEIRE IOSHIE; SARAIVA CAMARA, NIELS OLSEN; ALMEIDA, RAFAEL RIBEIRO. Butyrate Attenuates Lung Inflammation by Negatively Modulating Th9 Cells. FRONTIERS IN IMMUNOLOGY, v. 10, JAN 29 2019. Web of Science Citations: 3.

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