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

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. © 2008 The Author(s).