Altered expression of major immune regulatory molecules in peripheral blood immune cells associated with breast cancer

Breast Cancer. 2017 Jan;24(1):111-120. doi: 10.1007/s12282-016-0682-7. Epub 2016 Mar 4.

Abstract

Background: The purpose of this study was to clarify the alterations of major immune regulators in peripheral blood mononuclear cells (PBMCs) of cancer patients and to analyze the association with the disease progression in breast cancer patients.

Methods: The study included 6 healthy volunteers (HVs), 12 primary breast cancer (PBC) patients, and 30 metastatic breast cancer (MBC) patients. The expression of immune regulators such as, CCR6, CD4, CD8, CD14, CD40, CD56, CD80, CTLA4, CXCR4, FOXP3, IDO-1, IDO-2, NKG2D, NRP-1, PD-1, and PD-L1 mRNA in PBMCs was measured by quantitative RT-PCR. Analysis of variance with contrasts was performed to find expression patterns of the three groups (HVs, PBC, MBC).

Results: We clarified the alterations of mRNA of major immune regulators PD-L1, FOXP3, CD80, CD40, and CD14 in PBMCs of cancer patients and the association of these alternations with disease progression. Furthermore, PD-L1 expression was correlated with serum interferon-γ production.

Conclusion: Our data suggested that mRNA expressions of PD-L1, FOXP3, CD80, CD40 and CD14 in PBMCs are affected by disease progression. Understanding the roles of these various interactions will be of importance to future studies aiming to uncover biomarkers for predicting response to immune therapy.

Keywords: Breast cancer; CD40 and PBMCs; CD80; PD-1; PD-L1.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / genetics*
  • B7-H1 Antigen / genetics
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / immunology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Female
  • Forkhead Transcription Factors / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interferon-gamma / blood
  • Interferon-gamma / genetics
  • Leukocytes, Mononuclear / immunology*
  • Middle Aged
  • Programmed Cell Death 1 Receptor / genetics
  • Prospective Studies
  • Transforming Growth Factor beta / blood
  • Transforming Growth Factor beta / genetics

Substances

  • Antigens, CD
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Transforming Growth Factor beta
  • Interferon-gamma