Characterization of antigen-presenting properties of tumour cells using virus-specific cytotoxic T lymphocytes

DCJ Spierings, E Agsteribbe, J Wilschut, A Huckriede*

*Corresponding author for this work

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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 far human neuroblastoma. Immunofluorescence analyses revealed low and moderate expression of MHC class I molecules D-d and K-k respectively. Nevertheless, infected NB41A3 cells were lysed efficiently by influenza-specific CTLs. These results demonstrate that all steps of the antigen-processing pathway function properly in the NE tumour cells, and that the limited MHC class I expression suffices far efficient recognition by CTLs. In addition, lysis of the NE 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. (C) 2000 Cancer Research campaign.

Original languageEnglish
Pages (from-to)1474-1479
Number of pages6
JournalBritish Jounal of Cancer
Volume82
Issue number8
DOIs
Publication statusPublished - Apr-2000

Keywords

  • tumour
  • antigen presentation
  • immunotherapy
  • influenza virus
  • MAJOR HISTOCOMPATIBILITY COMPLEX
  • BLASTOMA CELL-LINES
  • I GENE-EXPRESSION
  • INFLUENZA-A VIRUS
  • NEURO-BLASTOMA
  • MELANOMA-CELLS
  • N-MYC
  • MURINE NEUROBLASTOMA
  • DOWN-REGULATION
  • MHC

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