HLA-E/β2 microglobulin overexpression in colorectal cancer is associated with recruitment of inhibitory immune cells and tumor progression

Int J Cancer. 2012 Aug 15;131(4):855-63. doi: 10.1002/ijc.26453. Epub 2012 Apr 5.

Abstract

The host immune response plays a major role in colorectal carcinoma (CRC) progression. A mechanism of tumor immune escape might involve expression of the human leucocyte antigen (HLA)-E/β2m on tumor cells. The inhibitory effect of HLA-E/β2m on CD8+ cytotoxic T lymphocytes and natural killer (NK) cells is mediated by the main HLA-E receptor CD94/NKG2A. As the pathophysiological relevance of this mechanism in CRC remains unknown, this prompted us to examine, in situ, in a series of 80 CRC (i) the HLA-E and β2m coexpression by tumor cells, (ii) the density of CD8+, cytotoxic, CD244+ and NKP46+ intraepithelial tumor-infiltrating lymphocyte (IEL-TIL) and (iii) the expression of CD94/NKG2 receptor on IEL-TIL. These data were then correlated to patient survival. We provided (i) the in situ demonstration of HLA-E/β2m overexpression by tumor cells in 21% of CRC characterized by an overrepresentation of signet ring cell carcinomas, mucinous carcinomas and medullary carcinomas, (ii) the significant association between HLA-E/β2m overexpression by tumor cells and increased density of CD8+ cytotoxic, CD244+ and CD94+ IEL-TIL and (iii) finally, the unfavorable prognosis associated with HLA-E/β2m overexpression by tumor cells. Our findings show that HLA-E/β2m overexpression is a surrogate marker of poor prognosis and point to a novel mechanism of tumor immune escape in CRC in restraining inhibitory IEL-TIL.

MeSH terms

  • Aged
  • Antigens, CD / immunology
  • Biomarkers, Tumor / metabolism*
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Female
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Male
  • Prognosis
  • Survival Analysis
  • Tissue Array Analysis
  • Tumor Escape
  • beta 2-Microglobulin / metabolism*

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • HLA-E antigen
  • Histocompatibility Antigens Class I
  • beta 2-Microglobulin