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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

HPV16 Tumor Associated Macrophages Suppress Antitumor T Cell Responses

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Autor(es):
Lepique, Ana Paula [1] ; Perez Daghastanli, Katia Regina [2] ; Cuccovia, Iolanda Midea [2] ; Villa, Luisa Lina [1]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Sao Paulo Branch, Inst Canc Res, Lab Virol Ludwig, BR-01323903 Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-01498 Sao Paulo - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: Clinical Cancer Research; v. 15, n. 13, p. 4391-4400, JUL 1 2009.
Citações Web of Science: 78
Resumo

Purpose: High-risk human papillomavirus (HPV) is the main etiologic factor for cervical cancer. The severity of HPV-associated cervical lesions has been correlated to the number of infiltrating macrophages. The objective of this work is to characterize the role of tumor-associated macrophages (TAM) on the immune cellular response against the tumor. Experimental Design: We used the HPV16 E6- and E7-expressing TC-1 mouse tumor model to study the effect of TAM on T-cell function in vitro, and depleted TAM, using clodronate-containing liposomes, to characterize its role in vivo. Results: TAM, characterized by the positive expression of CD45, F4/80, and CD11b, formed the major population of infiltrating tumor cells. TAM displayed high basal Arginase I activity, producing interleukin-10 (IL-10); they were resistant to iNOSll activity induction, therefore reversion to M1 phenotype, when stimulated in vitro with lipopolysaccharide/IFN gamma, indicating an M2 phentoype. In cultures of isolated TAM, TAM induced regulatory phenotype, characterized by IL-10 and Foxp3 expression, and inhibited proliferation of CD8 lymphocytes. In vivo, depletion of TAM inhibited tumor growth and stimulated the infiltration of tumors by HPV16 E7(49-57)-specific CD8 lymphocytes, whereas depletion of Gr1(+) tumor-associated cells had no effect. Conclusions: M2-like macrophages infiltrate HPV16-associated tumors causing suppression of antitumor T-cell response, thus facilitating tumor growth. Depletion or phenotype alteration of this population should be considered in immunotherapy strategies. (AU)

Processo FAPESP: 04/00749-2 - Interação entre HPV e o sistema imunológico em camundongos RAG-/- reconstituídos com células hematopoiéticas selvagens
Beneficiário:Ana Paula Lepique
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores