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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.)

Monocyte-derived dendritic cells from breast cancer patients are biased to induce CD4(+)CD25(+)Foxp3(+) regulatory T cells

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Autor(es):
Ramos, Rodrigo Nalio ; Chin, Lilian Sally ; dos Santos, Ana Paula S. A. [1] ; Bergami-Santos, Patricia Cruz ; Laginha, Fabio [2] ; Barbuto, Jose Alexandre M. [3]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Fed Maranhao, Dept Physiol, Ma - Brazil
[2] Perola Byngton Hosp, Dept Radiol, Sao Paulo - Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Lab Tumor Immunol, Dept Immunol, BR-05508900 Sao Paulo - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Journal of Leukocyte Biology; v. 92, n. 3, p. 673-682, SEP 2012.
Citações Web of Science: 38
Resumo

DCs orchestrate immune responses contributing to the pattern of response developed. In cancer, DCs may play a dysfunctional role in the induction of CD4(+)CD25(+) Foxp3(+) Tregs, contributing to immune evasion. We show here that Mo-DCs from breast cancer patients show an altered phenotype and induce preferentially Tregs, a phenomenon that occurred regardless of DC maturation stimulus (sCD40L, cytokine cocktail, TNF-alpha, and LPS). The Mo-DCs of patients induced low proliferation of allogeneic CD3(+)CD25(neg)Foxp3(neg) cells, which after becoming CD25(+), suppressed mitogen-stimulated T cells. Contrastingly, Mo-DCs from healthy donors induced a stronger proliferative response, a low frequency of CD4(+)CD25(+)Foxp3(+) with no suppressive activity. Furthermore, healthy Mo-DCs induced higher levels of IFN-gamma, whereas the Mo-DCs of patients induced higher levels of bioactive TGF-beta 1 and IL-10 in cocultures with allogeneic T cells. Interestingly, TGF-beta 1 blocking with mAb in cocultures was not enough to completely revert the Mo-DCs of patients' bias toward Treg induction. Altogether, these findings should be considered in immunotherapeutic approaches for cancer based on Mo-DCs. J. Leukoc. Biol. 92: 673-682; 2012. (AU)

Processo FAPESP: 09/02074-6 - Investigação de um possível viés imunossupressor em células dendríticas derivadas de indivíduos portadores de câncer
Beneficiário:Rodrigo Nalio Ramos
Linha de fomento: Bolsas no Brasil - Mestrado
Processo FAPESP: 09/54599-5 - Células dendríticas: elementos integrados do sistema imune - enfoque aplicado
Beneficiário:Jose Alexandre Marzagão Barbuto
Linha de fomento: Auxílio à Pesquisa - Temático