Circulating CD3+CD8+ T Lymphocytes as Indicators of Disease Status in Patients With Early Breast Cancer

Cancer Med. 2025 Jan;14(1):e70547. doi: 10.1002/cam4.70547.

Abstract

Circulating CD3+CD8+ cell levels were lower in breast cancer patients, elevated posttreatment, and subsequently declining upon recurrence. Elevated plasma chemokine (C-C motif) ligand 2 (CCL2) levels distinguished patients with breast cancer from healthy controls. In summary, circulating CD3+CD8+ CTL and plasma CCL2 levels emerged as promising dual-purpose biomarkers and therapeutic targets in breast cancer management.

Background: Identifying breast cancer markers with superior sensitivity, cost‐effectiveness, and practicality is imperative. Circulating immune cells and plasma cytokines hold promise as potential breast cancer markers.

Aims: To search and validate subtype of circulating immune cells and plasma cytokines as biomarkers for breast cancer patients.

Materials & methods: Using flow cytometry, we investigated circulating immune cell profiles in patients with breast cancer and healthy controls. To validate clinical observations, an orthotopic breast cancer model was established.

Results: We analyzed 19 healthy controls and 27 patients (22 testing group and 5 validation group) with breast cancer and revealed distinct populations, including CD3+CD4+ T lymphocytes, cytotoxic T lymphocytes (CTLs; CD3+CD8+), polymorphonuclear myeloid‐derived suppressor cells (PMN‐MDSCs), and monocytic (M)‐myeloid‐derived suppressive cells. Patients with breast cancer exhibited reduced CD3+CD4+ T lymphocyte, CD3+CD8+ CTL, and CD33+CD15− M‐MDSC levels compared with healthy controls. Diminished CD3+CD8+ CTL levels correlated with advanced cancer grade, extensive intraductal components, and positive lymphatic tumor emboli. Treatment effects included decreased T lymphocyte/PMN‐MDSC levels, contrasting with elevated circulating CD3+CD8+ cell levels posttreatment, subsequently declining upon recurrence in the validation group. Elevated plasma chemokine (C–C motif) ligand 2 (CCL2) levels distinguished patients with breast cancer from healthy controls. Our orthotopic model supported decreased circulating CD3+CD8+ CTL levels in cancer‐bearing mice, followed by a postresection increase.

Discussion: We found that circulating CD3+CD8+ CTL levels decreased in patients with breast cancer, increased after treatment, and decreased again upon recurrence.

Conclusion: Circulating CD3+CD8+ CTL emerged as promising prognostic biomarkers and therapeutic targets in breast cancer management.

Keywords: CCL2; biomarker; breast cancer; circulating immune cells; cytotoxic T lymphocytes.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor* / blood
  • Breast Neoplasms* / blood
  • Breast Neoplasms* / immunology
  • CD3 Complex* / blood
  • CD3 Complex* / metabolism
  • CD8-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / metabolism
  • Case-Control Studies
  • Chemokine CCL2 / blood
  • Female
  • Humans
  • Lymphocyte Count
  • Middle Aged
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Staging

Substances

  • CD3 Complex
  • Biomarkers, Tumor
  • Chemokine CCL2
  • CCL2 protein, human