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


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.


CONCLUSIONS
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.
Gerontology Department and Frailty in Aging Research (FRIA) Group, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
Oscar Okwudiri
OO
Onyema
Department of Medical Oncology, Oncology Center, UZ Brussel & Vrije Universiteit Brussel, Brussels, Belgium.
Lore
L
Decoster
Gerontology Department and Frailty in Aging Research (FRIA) Group, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
Rose
R
Njemini
Gerontology Department and Frailty in Aging Research (FRIA) Group, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
Louis Nuvagah
LN
Forti
Gerontology Department and Frailty in Aging Research (FRIA) Group, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
Ivan
I
Bautmans
Laboratory of Hematology, UZ Brussel, Brussels, Belgium.
Marc
M
De Waele
Gerontology Department and Frailty in Aging Research (FRIA) Group, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium Department of Geriatrics, UZ Brussel, Brussels, Belgium tmets@vub.ac.be.
Tony
T
Mets
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology; D018106:CD28 Antigens / Q000032:analysis; D018959:CD57 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016922:Cellular Senescence / Q000187:drug effects*; D004249:DNA Damage; D005260:Female; D006801:Humans; D008875:Middle Aged
D018106:CD28 Antigens; D018959:CD57 Antigens
CD28; CD57; breast cancer; cellular senescence; chemotherapy; immunosenescence