title: Tolerance or immunity to a tumor antigen expressed in somatic cells can be determined by systemic proinflammatory signals at the time of first antigen exposure.
abstract: Mice transgenic for the E7 tumor Ag of human papillomavirus type 16, driven from a keratin 14 promoter, express E7 in keratinocytes but not dendritic cells. Grafted E7-transgenic skin is not rejected by E7-immunized mice that reject E7-transduced transplantable tumors. Rejection of recently transplanted E7-transgenic skin grafts, but not of control nontransgenic grafts or of established E7-transgenic grafts, is induced by systemic administration of live or killed Listeria monocytogenes or of endotoxin. Graft recipients that reject an E7 graft reject a subsequent E7 graft more rapidly and without further L. monocytogenes exposure, whereas recipients of an E7 graft given without L. monocytogenes do not reject a second graft, even if given with L. monocytogenes. Thus, cross-presentation of E7 from keratinocytes to the adaptive immune system occurs with or without a proinflammatory stimulus, but proinflammatory stimuli at the time of first cross-presentation of Ag can determine the nature of the immune response to the Ag. Furthermore, immune effector mechanisms responsible for rejection of epithelium expressing a tumor Ag in keratinocytes are different from those that reject an E7-expressing transplantable tumor. These observations have implications for immunotherapy for epithelial cancers.
authors.affiliation: Centre for Immunology and Cancer Research, University of Queensland, Brisbane, Australia. ifrazer@medicine.pa.uq.edu.au
authors.forename: I H
authors.initials: IH
authors.lastname: Frazer
authors.forename: R
authors.initials: R
authors.lastname: De Kluyver
authors.forename: G R
authors.initials: GR
authors.lastname: Leggatt
authors.forename: H Y
authors.initials: HY
authors.lastname: Guo
authors.forename: L
authors.initials: L
authors.lastname: Dunn
authors.forename: O
authors.initials: O
authors.lastname: White
authors.forename: C
authors.initials: C
authors.lastname: Harris
authors.forename: A
authors.initials: A
authors.lastname: Liem
authors.forename: P
authors.initials: P
authors.lastname: Lambert
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D007275:Injections, Intravenous; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D008088:Listeriosis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology / Q000379:methods; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D000942:Antigens, Bacterial; D000951:Antigens, Neoplasm; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16