Human leukocyte antigen-E protein is overexpressed in primary human colorectal cancer

Int J Oncol. 2008 Mar;32(3):633-41.

Abstract

HLA-E is a non-classical MHC molecule whose expression by tumour cells has been recently reported in several human cancer types. We studied HLA-E expression in colorectal cancer patients, its clinical significance and prognostic value, as well as characterized its expression in colorectal cancer cell lines. We analysed HLA-E expression at the transcript level by qRT-PCR in micro-dissected samples and at the protein level by semiquantitative immunohistochemistry on paraffin-embedded tissue sections from 42 biopsies of colorectal cancer patients. We observed that HLA-E transcript and protein are spontaneously overexpressed in a significant proportion of colorectal tumour biopsies, as compared to normal mucosae. We also found a negative correlation between HLA-E expression and the CD57+ cells infiltrate. Moreover, we analysed HLA-E expression in several colorectal cancer cell lines and demonstrated that IFN-gamma upregulates the expression of membrane HLA-E in vitro. Interestingly, we demonstrated that colorectal cancer cell lines overexpressing HLA-E at the cell surface inhibited NK-mediated cell lysis. Although IFN-gamma regulatory role needs further investigation, we provide evidence suggesting that this cytokine, within the tumour microenvironment, could promote HLA-E translocation to the surface of tumour epithelial cells. Furthermore, we showed that upregulation of HLA-E could be a marker of shorter disease-free survival in Dukes' C patients and we suggest that this molecule renders tumours less susceptible to immune attack.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Caco-2 Cells
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Carcinoma / therapy
  • Cell Culture Techniques
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • HLA Antigens / metabolism*
  • HT29 Cells
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Killer Cells, Natural / drug effects
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Protein Transport
  • Recombinant Proteins / pharmacology
  • Tumor Cells, Cultured
  • Up-Regulation*
  • beta 2-Microglobulin / pharmacology

Substances

  • HLA Antigens
  • HLA-E antigen
  • Histocompatibility Antigens Class I
  • Recombinant Proteins
  • beta 2-Microglobulin