Chemotherapy-induced changes and immunosenescence of CD8+ T-cells in patients with breast cancer

Anticancer Res. 2015 Mar;35(3):1481-9.

Abstract

Background: Changes in sub-populations of cytotoxic (CD8+) T-cells, which are observed in aging and in conditions of chronic immune stimulation, are not well-documented in cancer.

Materials and methods: Using flow cytometry, CD8+ T-cell subsets were analyzed in patients with breast cancer undergoing DNA-damaging chemotherapy and in an older female control group during a six-month longitudinal study, to explore shifts in CD8+ T-cells and the effect of DNA-damaging chemotherapy on different T-cell sub-populations.

Results: As expected, there was a consistent decrease in absolute numbers of leukocytes, lymphocytes, T-cells and CD8+ T-cells during chemotherapy in patients with cancer. Among the T-cells, there was a lower CD8-/CD8+ ratio, persisting over the six months, in patients with cancer compared to controls. The proportion of CD28-CD57+ cells also remained higher among patients with cancer throughout the sampling duration. The number of CD28+CD57- and CD28-CD5- cells decreased faster during DNA-damaging chemotherapy than CD28+CD57+ and CD28-CD57+ cells, while only CD28-CD57- cells showed a significant reconstitutive capacity after six months.

Conclusion: Immunosenescence appeared to be pronounced in patients with breast cancer, with senescent CD8+ T-cells playing a role. The normal condition was not restored after six months of chemotherapy.

Keywords: CD28; CD57; breast cancer; cellular senescence; chemotherapy; immunosenescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / immunology
  • CD28 Antigens / analysis
  • CD57 Antigens / analysis
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • Cellular Senescence / drug effects*
  • DNA Damage
  • Female
  • Humans
  • Middle Aged

Substances

  • CD28 Antigens
  • CD57 Antigens