期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 45, 期 4, 页码 999-1009出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201444625
关键词
Adoptive Immunotherapy; B cells; Cytotoxicity; Fas; IL-10; Tumor
类别
资金
- NIH [CA82529]
- Gillson Longenbaugh Foundation
- National Science Fund of China [30971112]
- National Outstanding Youth Foundation of China [81025008]
- National Natural Science Foundation of China [31221061, 31270176]
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.
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