title: Characterization of antigen-presenting properties of tumour cells using virus-specific cytotoxic T lymphocytes.
abstract: Immunotherapy of tumours by induction of tumour-specific cytotoxic T-lymphocytes (CTLs) will only be effective for tumours with a functional antigen processing and presentation machinery. However, many tumours are known to down-regulate expression of major histocompatibility complex (MHC) class I molecules and/or to impair antigen processing. It is therefore desirable to evaluate the ability of a given tumour to present antigenic epitopes before developing an immunotherapy protocol. In this study we have used influenza virus as a tool to determine the antigen-presenting capacities of the murine neuroblastoma C1300 cell line NB41A3, a frequently used model for human neuroblastoma. Immunofluorescence analyses revealed low and moderate expression of MHC class I molecules Dd and Kk respectively. Nevertheless, infected NB41 A3 cells were lysed efficiently by influenza-specific CTLs. These results demonstrate that all steps of the antigen-processing pathway function properly in the NB tumour cells, and that the limited MHC class I expression suffices for efficient recognition by CTLs. In addition, lysis of the NB tumour cells shows that the cells are susceptible to CTL-induced apoptosis, a pathway that is often impaired in tumour cells. These characteristics make neuroblastoma a suitable target for immunotherapy. The presented assay allows evaluation of various immunological properties of tumour cells and, thus, represents a valuable tool to assess whether a given tumour will be susceptible to immunotherapy or not.
authors.affiliation: Department of Medical Microbiology, University of Groningen, The Netherlands.
authors.forename: D C
authors.initials: DC
authors.lastname: Spierings
authors.forename: E
authors.initials: E
authors.lastname: Agsteribbe
authors.forename: J
authors.initials: J
authors.lastname: Wilschut
authors.forename: A
authors.initials: A
authors.lastname: Huckriede
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D005260:Female; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology; D007739:L Cells; D051379:Mice; D008805:Mice, Inbred A; D009447:Neuroblastoma / Q000276:immunology* / Q000628:therapy*; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014407:Tumor Cells, Cultured
chemical_list: D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins; D007371:Interferon-gamma