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

被引:343
作者
Leffers, Ninke [1 ]
Gooden, Marloes J. M. [1 ]
de Jong, Renske A. [1 ]
Hoogeboom, Baukje-Nynke [1 ,2 ]
ten Hoor, Klaske A. [1 ]
Hollema, Harry [3 ]
Boezen, H. Marieke [4 ]
van der Zee, Ate G. J. [1 ]
Daemen, Toos [2 ]
Nijman, Hans W. [1 ]
机构
[1] Univ Groningen, Univ Med Ctr Groningen, Dept Gynecol Oncol, NL-9700 RB Groningen, Netherlands
[2] Univ Groningen, Univ Med Ctr Groningen, Mol Virol Sect, Dept Med Microbiol, NL-9700 RB Groningen, Netherlands
[3] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol, NL-9700 RB Groningen, Netherlands
[4] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 RB Groningen, Netherlands
关键词
Ovarian cancer; Memory T-lymphocytes; Omental metastasis; TISSUE MICROARRAYS; COLORECTAL-CANCER; CELL CARCINOMA; SURVIVAL; STATISTICS; LYMPHOMA; LOCATION; MELANOMA; FOXP3; HEAD;
D O I
10.1007/s00262-008-0583-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. 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. 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. 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.
引用
收藏
页码:449 / 459
页数:11
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