Higher human lymphocyte antigen class I expression in early-stage cancer cells leads to high sensitivity for cytotoxic T lymphocytes

Cancer Sci. 2019 Jun;110(6):1842-1852. doi: 10.1111/cas.14022. Epub 2019 May 18.

Abstract

Human lymphocyte antigen (HLA) class I molecules play a central role in cytotoxic T lymphocytes (CTL)-based antitumor immunity. However, the expression rate of HLA class I in cancer cells remains a topic of discussion. We compared HLA class I expression levels between cancer cells and surrounding non-tumorous hepatocytes in 20 early-stage hepatocellular carcinoma (HCC) patients by immunohistochemistry using EMR 8-5. The expression levels of HLA class I were classified as negative, incomplete positive or complete positive. Similarly, for various types of solid cancers, HLA class I expression was examined. For the HLA class I expression in cancer cells, among 20 HCC patients, 13 were complete positive, 3 were incomplete positive, and 4 were negative. In addition, 15 (75.0%) had higher expression levels of HLA class I in cancer cells compared with that in surrounding non-tumorous hepatocytes. An interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT) assay indicated that cancer cells with positive expression of HLA class I had strong sensitivity to antigen-specific CTL. We suggested that HLA class I expression in cancer cells could be involved in the clinical prognosis of HCC patients. Similarly, 66.7%, 100.0%, 66.7% and 62.5% of patients with early-stage pancreatic, gallbladder, esophageal and breast cancers, respectively, had higher expression levels of HLA class I in cancer cells than in surrounding normal tissue cells. We suggest that in several early-stage solid cancers, including HCC, HLA class I expression levels in cancer cells are higher than that in surrounding normal tissue cells, which could result in the anti-tumor effect of CTL-based cancer immunotherapy.

Keywords: EMR 8-5 antibody; cytotoxic T lymphocytes; hepatocellular carcinoma; human lymphocyte antigen class I expression; immunohistochemistry.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Female
  • HLA Antigens / biosynthesis
  • HLA Antigens / immunology*
  • Histocompatibility Antigens Class I / biosynthesis
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism

Substances

  • HLA Antigens
  • Histocompatibility Antigens Class I