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

Br J Cancer. 2000 Apr;82(8):1474-9. doi: 10.1054/bjoc.1999.1135.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Female
  • Genes, MHC Class I
  • Histocompatibility Antigens Class I / analysis
  • Humans
  • Influenza A virus / immunology*
  • Interferon-gamma / pharmacology
  • L Cells
  • Mice
  • Mice, Inbred A
  • Neuroblastoma / immunology*
  • Neuroblastoma / therapy*
  • Recombinant Proteins
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / virology
  • Tumor Cells, Cultured

Substances

  • Histocompatibility Antigens Class I
  • Recombinant Proteins
  • Interferon-gamma