HLA class I antigen expression is associated with a favorable prognosis in early stage non-small cell lung cancer

Cancer Sci. 2007 Sep;98(9):1424-30. doi: 10.1111/j.1349-7006.2007.00558.x. Epub 2007 Jul 23.


Human leukocyte antigen (HLA) class I displays a repertoire of endogenously processed peptides to CD8(+) T lymphocytes. The present study assessed correlations between HLA class I expression, clinicopathologic factors, and tumor-infiltrating immune cells in human non-small cell lung cancers (NSCLC). Expression of HLA class I was assessed in 161 resected primary NSCLC by immunohistochemistry using EMR8-5, a novel monoclonal anti-pan HLA class I heavy chain antibody. Expression of HLA class I was classified into three categories: strongly positive, weakly positive, or negative. Tumor-infiltrating CD8(+) lymphocytes and CD56(+) natural killer cells within cancer nests and stroma were also counted. Expression of HLA class I was strongly positive in 50 tumors, weakly positive in 57 tumors, and negative in 54 tumors. Down-regulation of HLA class I was significantly correlated with male sex, history of smoking, non-adenocarcinoma histology, and moderate-/low-grade differentiation. The density of cancer nest-infiltrating CD8(+) cells in HLA class I-negative tumors was significantly decreased compared to that in HLA class I strongly positive tumors (P < 0.01). Kaplan-Meier analysis revealed a significant favorable influence on overall survival for patients displaying tumors with strongly positive expression of HLA class I (P < 0.01). Multivariate analysis revealed down-regulation of HLA class I as an independent factor of poor prognosis in pathological stage I patients, but not in late-stage patients. These results suggest that down-regulation of HLA class I expression in NSCLC is a marker of poor prognosis, and this may play a critical role in immune surveillance of patients with NSCLC.

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / immunology*
  • HLA Antigens / biosynthesis*
  • HLA Antigens / genetics*
  • HLA Antigens / immunology
  • Histocompatibility Antigens Class I / biosynthesis*
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Prognosis
  • Retrospective Studies
  • beta 2-Microglobulin / biosynthesis
  • beta 2-Microglobulin / genetics


  • HLA Antigens
  • Histocompatibility Antigens Class I
  • beta 2-Microglobulin