Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Jandl, C.
Profiling of Neuroblastoma cell epitopes as target presentation on corresponding dendritic cells
[ Dissertation ] Medical University of Graz; 2010. pp. 39
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- Autor*innen der Med Uni Graz:
- Jandl Christoph
- Betreuer*innen:
- Birner-Grünberger Ruth
- Schwinger Wolfgang
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- Abstract:
- Neuroblastoma is the most common extracranial tumor of childhood originating from sympathetic neural crest cells. Amplification of the N-myc oncogene is an important predictor of poor prognosis. Existing therapies do not allow any treatment intensification because of the significant toxicity. In contrast, immune therapy seems to be more specific and potentially less toxic. To explore whether processing of neuroblastoma leads to tumor-specific epitope presentation by MHC class I molecules, immature dendritic cells were loaded with neuroblastoma cell lysates originating from the N-myc positive neuroblastoma cell line Kelly and the N-myc negative SK-N-AS. A further question was whether there was a difference in the pattern of antigen presentation between N-myc positive and N-myc negative neuroblastoma cell cultures. Distinct peptides were eluted from the surface of lysate pulsed dendritic cells and detected by mass spectroscopy. For MHC prediction studies, programs with different analyzation methods (SYFPEITHI , SVMHC and NetMHCIIpan ) were used to examine the identified peptides. Among them, seven predicted MHC class I and 23 MHC class II ligands were exclusively but not reproducibly found on tumor-lysate treated cells as compared to white blood cell-lysate or phosphate buffered saline treated cells. The higher total number of analyzed MHC peptides derived from white blood cell-lysate (n=131) as compared to phosphate buffered saline (n=11) treated controls suggests an uptake mechanism and/or a stimulation of enhanced MHC peptide presentation. In contrast to the MHC class II ligands, the identified MHC class I peptides appeared not to be of neuronal origin. Neither Kelly nor SK-N-AS treated maturated dendritic cells showed a detectable tumor specific pattern of MHC epitopes. Therefore no significant difference between N-myc positive or negative cell lines was detectable. In conclusion our data do not support a reproducible pattern of neuroblastoma mediated MHC class I peptide presentation, suggesting that the cytotoxic T-cell system may play a minor role in the immunological defense against neuroblastoma.