title: Antitumor effector B cells directly kill tumor cells via the Fas/FasL pathway and are regulated by IL-10.
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.
authors.affiliation: 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.
authors.forename: Huimin
authors.initials: H
authors.lastname: Tao
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.forename: Yang
authors.initials: Y
authors.lastname: Xia
authors.forename: Fu
authors.initials: F
authors.lastname: Dai
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Yangyi
authors.initials: Y
authors.lastname: Bao
authors.forename: Steven K
authors.initials: SK
authors.lastname: Lundy
authors.forename: Fumito
authors.initials: F
authors.lastname: Ito
authors.forename: Qin
authors.initials: Q
authors.lastname: Pan
authors.forename: Xiaolian
authors.initials: X
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
authors.forename: Guoshun
authors.initials: G
authors.lastname: Shu
authors.forename: Bingmu
authors.initials: B
authors.lastname: Fang
authors.forename: Jinhong
authors.initials: J
authors.lastname: Jiang
authors.forename: Jianchuang
authors.initials: J
authors.lastname: Xia
authors.forename: Shiang
authors.initials: S
authors.lastname: Huang
authors.forename: Qiao
authors.initials: Q
authors.lastname: Li
authors.forename: Alfred E
authors.initials: AE
authors.lastname: Chang
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D053222:Fas Ligand Protein / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D016219:Immunotherapy, Adoptive; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D019014:fas Receptor; D016753:Interleukin-10
keywords: Adoptive Immunotherapy; B cells; Cytotoxicity; Fas; IL-10; Tumor