Media type: E-Article 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 Contributor: Penafuerte, Claudia; Ng, Spencer; Bautista-Lopez, Norma; Birman, Elena; Forner, Kathy; Galipeau, Jacques imprint: American Association for Cancer Research (AACR), 2012 Published in: Cancer Research Language: English DOI: 10.1158/0008-5472.can-11-1659 ISSN: 0008-5472; 1538-7445 Keywords: Cancer Research ; Oncology Origination: Footnote: Description: <jats:title>Abstract</jats:title><jats:p>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. Cancer Res; 72(5); 1210–20. ©2012 AACR.</jats:p> Access State: Open Access