title: Absolute lymphocyte count is associated with survival in ovarian cancer independent of tumor-infiltrating lymphocytes.
abstract: BACKGROUND
  The immune system strongly influences outcome in patients with ovarian cancer. In particular, the absolute lymphocyte count in peripheral blood (ALC) and the presence of tumor-infiltrating lymphocytes (TIL) have each been associated with favourable prognosis. However, the mechanistic relationships between ALC, TIL and prognosis are poorly understood. We hypothesized that high ALC values might be associated with stronger tumor immunity as manifested by increased TIL, decreased tumor burden and longer survival.
  
  
  METHODS
  ALC values were collected from patient records ≥ 2 years before, during or after primary treatment for high-grade serous ovarian cancer (HGSC). Lymphocyte subsets were assessed in peripheral blood by flow cytometry. CD8+ and CD20+ TIL were assessed by immunohistochemistry.
  
  
  RESULTS
  Overall, patients had normal ALC values two or more years prior to diagnosis of HGSC. These values were not predictive of disease severity or survival upon subsequent development of HGSC. Rather, ALC declined upon development of HGSC in proportion to disease burden. This decline involved all lymphocyte subsets. ALC increased following surgery, remained stable during chemotherapy, but rarely recovered to pre-diagnostic levels. ALC values recorded at diagnosis did not correlate with CD8+ or CD20+ TIL but were associated with progression-free survival.
  
  
  CONCLUSIONS
  Patients with high intrinsic ALC values show no clinical or survival advantage upon subsequent development of HGSC. ALC values at diagnosis are prognostic due to an association with disease burden rather than TIL. Therapeutic enhancement of ALC may be necessary but not sufficient to improve survival in HGSC.
authors.affiliation: Trev and Joyce Deeley Research Centre, BC Cancer Agency, Victoria, BC, Canada.
authors.forename: Katy
authors.initials: K
authors.lastname: Milne
authors.forename: Cheryl
authors.initials: C
authors.lastname: Alexander
authors.forename: John R
authors.initials: JR
authors.lastname: Webb
authors.forename: Winnie
authors.initials: W
authors.lastname: Sun
authors.forename: Kristy
authors.initials: K
authors.lastname: Dillon
authors.forename: Steve E
authors.initials: SE
authors.lastname: Kalloger
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.forename: Blaise
authors.initials: B
authors.lastname: Clarke
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
authors.forename: Brad H
authors.initials: BH
authors.lastname: Nelson
mesh_terms: D015331:Cohort Studies; D017281:Cost of Illness; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D060787:Neoplasm Grading; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000601:surgery; D009504:Neutrophils / Q000276:immunology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome