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

Br J Cancer. 2012 Jun 5;106(12):1980-8. doi: 10.1038/bjc.2012.197. Epub 2012 May 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / genetics*
  • Carcinoma
  • Cell Line, Tumor
  • Epithelial Cells / immunology
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Interleukin-6 / metabolism
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • Up-Regulation
  • Viral Matrix Proteins / metabolism*

Substances

  • EBV-associated membrane antigen, Epstein-Barr virus
  • Histocompatibility Antigens Class I
  • Interleukin-6
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Viral Matrix Proteins