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Eur J Immunol ; 45(4): 999-1009, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25545618

RESUMO

We have previously reported that adoptive transfer of tumor-draining lymph node (TDLN) B cells confers tumor regression in a spontaneous pulmonary metastasis mouse model of breast cancer. In this study, we identified IL-10-producing cells within these B cells, and found that IL-10 removal, either by using IL-10(-/-) TDLN B cells or by systemic neutralization of IL-10, significantly augmented the therapeutic efficacy of adoptively transferred TDLN B cells. Depletion of IL-10 in B-cell adoptive transfers significantly increased CTLs and B-cell activity of PBMCs and splenic cells in the recipient. Activated TDLN B cells express Fas ligand, which was further enhanced by coculture of these TDLN B cells with 4T1 tumor cells. Effector B cells killed tumor cells directly in vitro in an antigen specific and Fas ligand-dependent manner. Trafficking of TDLN B cells in vivo suggested that they were recruited to the tumor and lung as well as secondary lymphoid organs. These findings further define the biological function of antitumor effector B cells, which may offer alternative cellular therapies to cancer.


Assuntos
Subpopulações de Linfócitos B/imunologia , Proteína Ligante Fas/biossíntese , Imunoterapia Adotiva , Interleucina-10/imunologia , Neoplasias/terapia , Linfócitos T Citotóxicos/imunologia , Animais , Subpopulações de Linfócitos B/transplante , Linhagem Celular Tumoral , Movimento Celular/imunologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Proteína Ligante Fas/imunologia , Feminino , Interleucina-10/genética , Linfonodos/imunologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Neoplasias/imunologia , Receptor fas/imunologia
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