c-Myc and EBV–LMP1: two opposing regulators of the HLA class I antigen presentation machinery in epithelial cells

Background: Epstein–Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) up-regulates the human leukocyte antigen (HLA) class I antigen presentation machinery (APM). This appears counterintuitive with immune evasion in EBV-associated tumours like nasopharyngeal carcinoma (NPC). Methods: Latent...

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Bibliographic Details
Published in:British journal of cancer 2012-06, Vol.106 (12), p.1980-1988
Main Authors: Tudor, C S, Dawson, C W, Eckhardt, J, Niedobitek, G, Büttner, A C, Seliger, B, Hartmann, A, Buettner, M
Format: Article
Language:English
Subjects:
631/208/199
631/250/2161
692/699/67/1536
Antigen presentation
Antigen Presentation - genetics
Biomedical and Life Sciences
Biomedicine
Cancer Research
Carcinoma
Cell Line, Tumor
Drug Resistance
Epidemiology
Epithelial Cells - immunology
Epstein-Barr virus
Histocompatibility Antigens Class I - metabolism
Humans
Interleukin-6 - metabolism
Kinases
Leukocytes
Medical research
Molecular Diagnostics
Molecular Medicine
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms - genetics
Oncology
Peptides
Proteins
Proto-Oncogene Proteins c-myc - metabolism
Signal Transduction
STAT3 Transcription Factor - metabolism
Tumors
Up-Regulation
Viral Matrix Proteins - metabolism
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Summary:Background: Epstein–Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) up-regulates the human leukocyte antigen (HLA) class I antigen presentation machinery (APM). This appears counterintuitive with immune evasion in EBV-associated tumours like nasopharyngeal carcinoma (NPC). Methods: Latent membrane protein 1-transfected epithelial cell lines were used as a model system to study the impact of LMP1 and c-Myc on HLA class I components. The expression of components of the HLA class I APM, c-Myc and Ki-67 was analysed in LMP1+ and LMP1− NPC by immunohistochemistry. Results: In epithelial cells, LMP1 up-regulated HLA class I APM. This effect could be counteracted by c-Myc, which itself was up-regulated by LMP1 apparently through IL6 induction and Jak3/STAT3 activation. Studies of NPC biopsies revealed down-regulation of HLA class I APM expression. No difference was observed between LMP1+ and LMP1− NPC. However, expression of Ki-67 and c-Myc were up-regulated in LMP1+ tumours. Conclusion: These findings raise the possibility that c-Myc activation in NPC might antagonise the effect of LMP1 on HLA class I expression thus contributing to immune escape of tumour cells.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2012.197