CD25(+) T cell depletion impairs murine squamous cell carcinoma development via modulation of antitumor immune responses
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
14/10/2013
14/10/2013
2012
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Resumo |
Squamous cell carcinoma (SCC) constitutes a microenvironment that could modulate the antitumor immune response. Also, tumor-infiltrating lymphocytes are believed to play complex regulatory roles in antitumor immunity against SCC. The presence of regulatory T cells (Tregs) has been associated with the suppression of tumor-reactive T cells. However, the underlying mechanism for this T cell dysfunction is not clear. We used a multistage model of SCC to examine the role of Treg cells during tumor development. 7,12-dimethylbenz[a]-anthracene/phorbol 12-myristate 13-acetate treatment and systemic depletion of Treg cells using an anti-CD25 monoclonal antibody (PC61) resulted in a decrease in the number and incidence of papilloma. Furthermore, CD25 depletion increased the proportion of CD8(+) and CD4(+) T cells that were isolated from tumor lesions. The levels of interleukin (IL)-1 beta, IL-10, IL-12, IL-13, interferon-gamma, transforming growth factor-beta and tumor necrosis factor-alpha, but not IL-17, were increased in the tumor microenvironment after Treg depletion. Therefore, our results indicated involvement of CD25(+) T cells in SCC development and in the suppression of the inflammatory immune response. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2008/10999-7, 2012/03859-0, 2006/01617-8, 2009/14127-7, 2009/03471-9] Fundacao de Amparo a Pesquisa do Estado de Sao Paulo Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) Cientifico e Tecnologico (CNPq) Cientifico e Tecnologico (CNPq) |
Identificador |
CARCINOGENESIS, OXFORD, v. 33, n. 4, supl. 4, Part 1-2, pp. 902-909, APR, 2012 0143-3334 http://www.producao.usp.br/handle/BDPI/34314 10.1093/carcin/bgs103 |
Idioma(s) |
eng |
Publicador |
OXFORD UNIV PRESS OXFORD |
Relação |
CARCINOGENESIS |
Direitos |
closedAccess Copyright OXFORD UNIV PRESS |
Palavras-Chave | #TUMOR MICROENVIRONMENT #CANCER #GROWTH #THERAPY #HEAD #NECK #CARCINOGENESIS #IMMUNOTHERAPY #INACTIVATION #INFLAMMATION #ONCOLOGY |
Tipo |
article original article publishedVersion |