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 language | English |
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Pages (from-to) | 1474-1479 |
Number of pages | 6 |
Journal | British Jounal of Cancer |
Volume | 82 |
Issue number | 8 |
DOIs | |
Publication status | Published - 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