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

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

Ninke Leffers  1 , Marloes J M Gooden, Renske A de Jong, Baukje-Nynke Hoogeboom, Klaske A ten Hoor, Harry Hollema, H Marieke Boezen, Ate G J van der Zee, Toos Daemen, Hans W Nijman
Affiliations

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

Ninke Leffers et al. Cancer Immunol Immunother. 2009 Mar.

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.

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Figures

Fig. 1
Fig. 1
Immunohistochemical staining of tumor-infiltrating T-lymphocytes in ovarian cancer tissue. a Flow diagram showing the type of tissue analyzed and the percentage of patients lost from analysis. Patients were excluded from analysis when less than two tissue cores with at least 20% tumor were present for evaluation. b Intra-tumoral CD8+ T-lymphocytes, c CD45R0+ T-lymphocytes, d FoxP3+ T-lymphocytes at 400× magnification
Fig. 2
Fig. 2
Disease-specific survival (in months) of ovarian cancer patients based on tumor-infiltrating lymphocytes. Cumulative survival time was estimated by the Kaplan–Meier method. Log Rank test was used to evaluate survival differences between groups. High numbers of CD8+ T-lymphocytes (a) and a high CD8+/Foxp3+ ratio (b) in ovarian-derived tumor tissue were associated with improved survival in FIGO stage I–IV disease. In advanced stage patients, a survival benefit was observed for patients with CD45R0+ T-lymphocytes (c) CD8+ T-lymphocytes (d), FoxP3+ T-lymphocytes (e) a high CD8+/FoxP3+ ratio (f) in ovarian-derived tumor tissue. Furthermore, FoxP3+ (g) and CD45R0+ T-lymphocytes (h) in omental metastases were associated with improved disease-specific survival
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