title: Elevated level of peripheral CD8(+)CD28(-) T lymphocytes are an independent predictor of progression-free survival in patients with metastatic breast cancer during the course of chemotherapy.
abstract: OBJECTIVE
  Suppression of cellular immunity resulting from tumorigenesis and/or therapy might promote cancer cells' growth, progression and invasion. Here, we explored whether T lymphocyte subtypes from peripheral blood of metastatic breast cancer (MBC) female patients could be used as alternative surrogate markers for cancer progress. Additionally, plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IFN-γ, and transforming growth factor-β1 were quantitated from MBC and healthy volunteers.
  
  
  METHODS
  This study included 89 female MBC patients during the post-salvage chemotherapy follow-up and 50 age- and sex-matched healthy volunteers as control. The percentages of T lymphocyte subpopulations from peripheral blood and plasma levels of cytokines were measured.
  
  
  RESULTS
  Both CD8(+)CD28(-) and CD4(+)CD25(+) were elevated in MBC patients compared to the control cohort (P < 0.05). In contrast, CD3(+) and CD8(+)CD28(+)cells were significantly lower in MBC patients (P < 0.0001, P = 0.045, respectively). MBC patients had elevated levels of immunosuppressive cytokines IL-6 and IL-10. Patients with elevated CD8(+)CD28(-) and CD4(+)CD25(+) cells showed increased levels of IL-6, and only patients with elevated CD8(+)CD28(-) had decreased interferon-γ. Univariate analysis indicated increased CD3(+)CD4(+) or CD8(+)CD28(+)correlated with prolonged progression-free survival (PFS), while elevated CD8(+)CD28(-)associated with shorten PFS. The percent of CD8(+)CD28(-) T lymphocytes is an independent predictor for PFS through multivariate analysis.
  
  
  CONCLUSIONS
  This study suggests that progressive elevated levels of CD8(+)CD28(-) suppressor T lymphocytes represent a novel independent predictor of PFS during post-chemotherapy follow-up.
authors.affiliation: Department of Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, 52 Fucheng Rd, Beijing 100142, China.
authors.forename: Guohong
authors.initials: G
authors.lastname: Song
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Jia
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Yuan
authors.forename: Fengling
authors.initials: F
authors.lastname: Wan
authors.forename: Xinna
authors.initials: X
authors.lastname: Zhou
authors.forename: Huabing
authors.initials: H
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.forename: Jiezhun
authors.initials: J
authors.lastname: Gu
authors.forename: Herbert Kim
authors.initials: HK
authors.lastname: Lyerly
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality* / Q000473:pathology; D018106:CD28 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D016022:Case-Control Studies; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D018655:Lymphocyte Count; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D018106:CD28 Antigens; D016827:CD8 Antigens; D016207:Cytokines