title: Hodgkin's lymphoma RNA-transfected dendritic cells induce cancer/testis antigen-specific immune responses.
abstract: Cytotoxic T lymphocytes (CTL) can kill Hodgkin's lymphoma (HL) cells, and CTL have been used for the treatment of Epstein-Barr virus (EBV)-positive HL. For patients with EBV-negative HL, this strategy cannot be employed and alternative target structures have to be defined. In order to establish a system for the stimulation of HL-reactive T cells, we used dendritic cells (DC) as antigen-presenting cells for autologous T cells and transfected these DC with RNA from established HL cell lines. After stimulation of peripheral blood mononuclear cells (PBMC) with RNA-transfected DC, we analyzed the reactivity of primed PBMC by interferon gamma enzyme-linked immunospot. Our results suggest the presence of antigens with expression in HL cell lines and recognition of these antigens in combination with DC-derived human leukocyte antigen molecules. By the analysis of Gene Expression Omnibus microarray data sets from HL cell lines and primary HL samples in comparison with testis and other normal tissues, we identified HL-associated cancer testis antigens (CTA) including the preferentially expressed antigen in melanoma (PRAME). After stimulation of PBMC with RNA-transfected DC, we detected PRAME-reactive T cells. PRAME and other HL-associated CTA might be targets for HL-specific immune therapy or for the monitoring of HL-directed immune responses.
authors.affiliation: Department of Pediatrics, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06097 Halle, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Winkler
authors.forename: Daniel Sebastian
authors.initials: DS
authors.lastname: Steingrube
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Altermann
authors.forename: Gerald
authors.initials: G
authors.lastname: Schlaf
authors.forename: Daniela
authors.initials: D
authors.lastname: Max
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kewitz
authors.forename: Alexander
authors.initials: A
authors.lastname: Emmer
authors.forename: Malte
authors.initials: M
authors.lastname: Kornhuber
authors.forename: Ursula
authors.initials: U
authors.lastname: Banning-Eichenseer
authors.forename: Martin Sebastian
authors.initials: MS
authors.lastname: Staege
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D058501:Enzyme-Linked Immunospot Assay; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000276:immunology / Q000378:metabolism; D013737:Testis / Q000276:immunology / Q000378:metabolism; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D012334:RNA, Neoplasm