title: Adoptive Transfer of Tumor-Specific Th2 Cells Eradicates Tumors by Triggering an In Situ Inflammatory Immune Response.
abstract: Adoptive cell therapy (ACT) trials to date have focused on transfer of autologous tumor-specific cytotoxic CD8+T cells; however, the potential of CD4+T helper (Th) cells for ACT is gaining interest. While encouraging results have been reported with IFNγ-producing Th1 cells, tumor-specific Th2 cells have been largely neglected for ACT due to their reported tumor-promoting properties. In this study, we tested the efficacy of idiotype-specific Th2 cells for the treatment of mice with MHC class II-negative myeloma. Th2 ACT efficiently eradicated subcutaneous myeloma in an antigen-specific fashion. Transferred Th2 cells persisted in vivo and conferred long-lasting immunity. Cancer eradication mediated by tumor-specific Th2 cells did not require B cells, natural killer T cells, CD8+T cells, or IFNγ. Th2 ACT was also curative against B-cell lymphoma. Upon transfer, Th2 cells induced a type II inflammation at the tumor site with massive infiltration of M2-type macrophages producing arginase. In vivo blockade of arginase strongly inhibited Th2 ACT, consistent with a key role of arginase and M2 macrophages in myeloma elimination by Th2 cells. These results illustrate that cancer eradication may be achieved by induction of a tumor-specific Th2 inflammatory immune response at the tumor site. Thus, ACT with tumor-specific Th2 cells may represent a highly efficient immunotherapy protocol against cancer. Cancer Res; 76(23); 6864-76. ©2016 AACR.
authors.affiliation: Centre for Immune Regulation, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Kristina Berg
authors.initials: KB
authors.lastname: Lorvik
authors.affiliation: K.G. Jebsen Inflammation Research Centre, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Clara
authors.initials: C
authors.lastname: Hammarström
authors.affiliation: Centre for Immune Regulation, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Marte
authors.initials: M
authors.lastname: Fauskanger
authors.affiliation: Centre for Immune Regulation, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Ole Audun Werner
authors.initials: OA
authors.lastname: Haabeth
authors.affiliation: Centre for Immune Regulation, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Michael
authors.initials: M
authors.lastname: Zangani
authors.affiliation: K.G. Jebsen Inflammation Research Centre, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Guttorm
authors.initials: G
authors.lastname: Haraldsen
authors.affiliation: Centre for Immune Regulation, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway.|K.G. Jebsen Centre for Influenza Vaccine Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
authors.affiliation: Centre for Immune Regulation, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway. alexandre.corthay@ibv.uio.no.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Corthay
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D018418:Th2 Cells / Q000276:immunology*