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

Immunotherapy of tumours by induction of tumour-specific cytotoxic T-lympho cytes (CTLs) will only be effective for tumours with a functional antigen p rocessing and presentation machinery. However, many tumours are known to do wn-regulate expression of major histocompatibility complex (MHC) class I mo lecules and/or to impair antigen processing. It is therefore desirable to e valuate 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 murin e neuroblastoma C1300 cell line NB41A3, a frequently used model far human n euroblastoma. Immunofluorescence analyses revealed low and moderate express ion of MHC class I molecules D-d and K-k respectively. Nevertheless, infect ed NB41A3 cells were lysed efficiently by influenza-specific CTLs. These re sults demonstrate that all steps of the antigen-processing pathway function properly in the NE tumour cells, and that the limited MHC class I expressi on 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 m ake 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 s usceptible to Immunotherapy or not. (C) 2000 Cancer Research campaign.