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Eur J Immunol ; 45(4): 999-1009, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25545618

ABSTRACT

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.


Subject(s)
B-Lymphocyte Subsets/immunology , Fas Ligand Protein/biosynthesis , Immunotherapy, Adoptive , Interleukin-10/immunology , Neoplasms/therapy , T-Lymphocytes, Cytotoxic/immunology , Animals , B-Lymphocyte Subsets/transplantation , Cell Line, Tumor , Cell Movement/immunology , Cell- and Tissue-Based Therapy/methods , Fas Ligand Protein/immunology , Female , Interleukin-10/genetics , Lymph Nodes/immunology , Lymphocyte Activation/immunology , Mice , Mice, Inbred BALB C , Mice, Knockout , Neoplasms/immunology , fas Receptor/immunology
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