Blood Cytokine Profile in Breast Cancer: Focusing on Differences among Molecular Subtypes

Iran J Immunol. 2024 Dec 31;21(4):316-327. doi: 10.22034/iji.2024.103582.2848. Epub 2024 Dec 25.

Abstract

Background: Breast cancer is the leading cause of cancer-related deaths in women. Cytokines have been linked to various cancers, and both benign and malignant breast diseases are associated with inflammation. However, there is limited understanding of how the immune system's cytokine response varies among different subtypes of breast cancer.

Objective: To assess cytokine levels in breast cancer patients according to their subtypes and investigate the potential role of these cytokines in treatment.

Methods: Patients with stage 1-2 breast cancer and healthy volunteers were included in the study. The breast cancer patients were classified as luminal A, luminal B, and triple negative based on ER, PR, HER2 receptor status, and Ki67 score of trucut biopsy results. Multiplex assay and flow cytometry were used to quantify the concentrations of IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p (p70), IL-17A, IL-18, IL-23, and IL-33 in serum samples collected from all participants. Age, menopausal status, and hematologic parameters were also compared between groups.

Results: The study involved 19 luminal A, 20 luminal B, 18 triple-negative patients and 21 healthy volunteers. TNF-α, IL-6, IL-8, IL-10, IL-12p (p70), IL-18, and IL-23 cytokines were significantly higher in breast cancer patients than in healthy volunteers. Significant differences in IFN-γ, IL-6, IL-8, IL-10, IL-12p (p70), IL-17A, IL-18, and IL-23 were observed between subtypes, with triple-negative patients showing lower cytokine levels, except for MCP-1.

Conclusion: The decreased levels of cytokines in triple-negative breast cancer indicate lower immunogenicity leading to more aggressive tumor progression as a result of an insufficient immune response.

Keywords: Breast Cancer; Cytokine; Inflammation; Triple Negative.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood
  • Breast Neoplasms* / blood
  • Breast Neoplasms* / diagnosis
  • Breast Neoplasms* / immunology
  • Cytokines* / blood
  • Cytokines* / metabolism
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Triple Negative Breast Neoplasms / blood
  • Triple Negative Breast Neoplasms / diagnosis
  • Triple Negative Breast Neoplasms / immunology

Substances

  • Cytokines
  • Biomarkers, Tumor