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




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Cancer Immunology, Immunotherapy

, 58:449

First Online: 13 September 2008Received: 11 June 2008Accepted: 21 August 2008

Abstract

PurposeOvarian 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 designThe 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.

ResultsHigh 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.

ConclusionsT-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.

KeywordsOvarian cancer Memory T-lymphocytes Omental metastasis Ninke Leffers and Marloes J. M. Gooden contributed equally.

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Author: Ninke Leffers - Marloes J. M. Gooden - Renske A. de Jong - Baukje-Nynke Hoogeboom - Klaske A. ten Hoor - Harry Hollema

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