Differential expression of major histocompatibility complex class I in subtypes of breast cancer is associated with estrogen receptor and interferon signaling

Oncotarget. 2016 May 24;7(21):30119-32. doi: 10.18632/oncotarget.8798.

Abstract

Tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC) have a strong prognostic and predictive significance. However, the mechanism of TIL influx in TNBC is unclear. Expression of major histocompatibility complex class I (MHC I) on the tumor cell is essential for the effective killing of tumor by cytotoxic TILs. In our current study, human leukocyte antigen (HLA) expression was inversely correlated with estrogen receptor (ER) expression in normal and cancerous breast tissue and positively correlated with TILs in breast cancer. The ER score was inversely correlated with TILs in breast cancer. HLA-A and CD8B gene expression was negatively correlated with ESR1 and positively correlated with interferon-associated gene expression in The Cancer Genome Atlas (TCGA) data. Negative correlation between ESR1 and HLA and positive correlation between interferon-associated and HLA gene expression were also confirmed in Cancer Cell Line Encyclopedia (CCLE) data. Taken together, our data suggest that a lower expression of HLA in luminal-type tumors might be associated with low level of TILs in those tumors. Further investigation of the mechanism of higher HLA expression and TIL influx in TNBC may help to boost the host immune response.

Keywords: Pathology Section; breast carcinoma; human leukocyte antigen; major histocompatibility complex I; tumor-infiltrating lymphocytes.

MeSH terms

  • Breast / pathology
  • CD8 Antigens / metabolism*
  • Cell Line, Tumor
  • Disease-Free Survival
  • Estrogen Receptor alpha / metabolism*
  • Female
  • HLA-A Antigens / immunology
  • HLA-A Antigens / metabolism*
  • HLA-B Antigens / immunology
  • HLA-B Antigens / metabolism*
  • HLA-C Antigens / immunology
  • HLA-C Antigens / metabolism*
  • Humans
  • Immunohistochemistry
  • Interferons / metabolism
  • Lymphatic Metastasis
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Mutation
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Progesterone / metabolism
  • Tissue Array Analysis
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / immunology*
  • Triple Negative Breast Neoplasms / mortality
  • Triple Negative Breast Neoplasms / pathology

Substances

  • CD8 Antigens
  • CD8beta antigen
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-C Antigens
  • Receptors, Progesterone
  • Interferons
  • ERBB2 protein, human
  • Receptor, ErbB-2