Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer

Cancer Immunol Immunother. 2009 Mar;58(3):449-59. doi: 10.1007/s00262-008-0583-5. Epub 2008 Sep 13.

Abstract

Purpose: Ovarian cancer patients with intra-tumoral CD3(+) T-lymphocytes in primary tumor tissue have a better prognosis. This study aims to analyze the presence and relative influence of three important T-lymphocyte subsets, tumor-infiltrating CD8(+) cytotoxic T-lymphocytes (CTL), CD45R0(+) memory T-lymphocytes, and FoxP3(+) regulatory T-lymphocytes (Treg), in primary tumor tissue and omental metastases of patients with ovarian cancer.

Experimental design: The number of CD8(+), CD45R0(+), and FoxP3(+) T-lymphocytes was determined by immunohistochemistry on a tissue micro array containing ovarian tumor tissue and/or omental metastases obtained at primary debulking surgery from 306 FIGO stage I-IV ovarian cancer patients. Immunohistochemistry data were correlated to clinicopathological parameters and survival data.

Results: High number of CD8(+) CTL and a high CD8(+)/FoxP3(+) ratio in ovarian-derived tumor tissue were associated with increased disease-specific survival and proved to be independent prognostic factors in multivariate analyses. In advanced stage patients, the presence of CD8(+) CTL, CD45R0(+) memory T-lymphocytes, FoxP3(+) Treg or a high CD8(+)/FoxP3(+) ratio in ovarian-derived tumor tissue was associated with an increased disease specific survival in univariate analysis, as was the presence of CD45R0(+) memory T-lymphocytes and FoxP3(+) Treg in omental metastases. Furthermore, in advanced stage patients CD8(+) cytotoxic and FoxP3(+) regulatory T-lymphocytes infiltrating ovarian-derived tumor tissue were independent predictors of increased prognosis.

Conclusions: T-lymphocytes infiltrating primary and metastatic ovarian cancer sites are associated with improved prognosis. These associations are especially distinct in advanced stage patients, underlining the potential for immunotherapy as a broadly applicable therapeutic strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD8-Positive T-Lymphocytes / metabolism
  • Female
  • Follow-Up Studies
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immunohistochemistry
  • Immunologic Memory
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Middle Aged
  • Neoplasm Metastasis
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Treatment Outcome

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors