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Eur J Immunol. 2015 Apr;45(4):999-1009. doi: 10.1002/eji.201444625. Epub 2015 Jan 21.

Antitumor effector B cells directly kill tumor cells via the Fas/FasL pathway and are regulated by IL-10.

Author information

1
Department of Surgery, University of Michigan, , Ann Arbor, MI, USA; Hubei Province Stem Cell Research and Appling Center, Institute of Hematology, , Union Hospital, , Tongji Medical College, , Huazhong University of Science and Technology, Wuhan, China.

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.

KEYWORDS:

Adoptive Immunotherapy; B cells; Cytotoxicity; Fas; IL-10; Tumor

PMID:
25545618
PMCID:
PMC4414939
DOI:
10.1002/eji.201444625
[Indexed for MEDLINE]
Free PMC Article

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