title: B effector cells activated by a chimeric protein consisting of IL-2 and the ectodomain of TGF-β receptor II induce potent antitumor immunity.
abstract: We have previously shown that interleukin (IL)-2 receptor-expressing lymphoid cells stimulated with a chimeric protein linking IL-2 to the ectodomain of TGF-β receptor II (also known as FIST) become resistant to TGF-β-mediated suppression and produce significant amounts of proinflammatory cytokines. In this study, we have characterized the antigen presentation properties of FIST-stimulated B cells (hereafter inducible B effector cells, iBEC). FIST converts naïve splenic B cells to B effector cells characterized by potent antigen presentation properties and production of TNFα and IFNγ. iBECs display hyperphosphorylation of STAT3 and STAT5 downstream of the IL-2 receptor and upregulation of T-bet expression. iBECs maintain B-cell identity based on the expression of PAX5 and CD19 and overexpress Smad7, which confers resistance to TGF-β-mediated suppression of B-cell activation. iBEC antitumor immunity was determined by a mouse model of lymphoma-expressing ovalbumin (E.G7-OVA) as a specific tumor antigen. OVA-pulsed iBECs function as antigen-presenting cells (APC) in vitro by inducing the activation of OVA-specific CD4(+) and CD8(+) T cells, respectively, and in vivo by conferring complete protective immunity against E.G7-OVA tumor challenge. In addition, OVA-pulsed iBECs promote tumor regression in immunocompetent C57Bl/6 mice bearing E.G7-OVA tumors. In conclusion, iBECs represent an entirely novel B cell-derived APC for immune therapy of cancer.
authors.affiliation: Department of Experimental Medicine, McGill University, Montreal, Canada.
authors.forename: Claudia
authors.initials: C
authors.lastname: Penafuerte
authors.forename: Spencer
authors.initials: S
authors.lastname: Ng
authors.forename: Norma
authors.initials: N
authors.lastname: Bautista-Lopez
authors.forename: Elena
authors.initials: E
authors.lastname: Birman
authors.forename: Kathy
authors.initials: K
authors.lastname: Forner
authors.forename: Jacques
authors.initials: J
authors.lastname: Galipeau
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D055786:Gene Knockout Techniques; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology
chemical_list: D007376:Interleukin-2; D011993:Recombinant Fusion Proteins