Abstract
BackgroundThe 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.MethodsALC 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.ResultsOverall, 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.ConclusionsPatients 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.
Highlights
The immune system strongly influences outcome in patients with ovarian cancer
absolute lymphocyte count in peripheral blood (ALC) declines upon the development of ovarian cancer To assess whether individuals with high intrinsic ALC values might experience a more favorable prognosis upon the development of High-grade serous epithelial ovarian cancer (HGSC), we studied a cohort of HGSC patients for whom we obtained matched ALC values recorded ≥ 2 years prior to diagnosis and at the time of diagnosis before any form of treatment
The mean pre-treatment ALC was significantly lower at 1.4 Giga/L (p < 0.0001 by Wilcoxon signed rank test), indicating that the development of HGSC is associated with a marked decline in ALC
Summary
The immune system strongly influences outcome in patients with ovarian cancer. The absolute lymphocyte count in peripheral blood (ALC) and the presence of tumor-infiltrating lymphocytes (TIL) have each been associated with favourable prognosis. We hypothesized that high ALC values might be associated with stronger tumor immunity as manifested by increased TIL, decreased tumor burden and longer survival. Current standard care for advanced HGSC is cytoreductive surgery and chemotherapy with In addition to these standard prognostic factors, the host immune response to ovarian cancer has a strong influence on clinical outcomes [3,4]. In addition to CD8+ T cells, CD20+ tumor-infiltrating B cells are associated with survival in HGSC [9] and other cancers [10]. As with many other human cancers, TIL and associated factors show a clear association with clinical outcomes in ovarian cancer
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