Abstract
BackgroundTumor-infiltrating T cells are associated with survival in epithelial ovarian cancer (EOC), but their functional status is poorly understood, especially relative to the different risk categories and histological subtypes of EOC.Methodology/Principal FindingsTissue microarrays containing high-grade serous, endometrioid, mucinous and clear cell tumors were analyzed immunohistochemically for the presence of lymphocytes, dendritic cells, neutrophils, macrophages, MHC class I and II, and various markers of activation and inflammation. In high-grade serous tumors from optimally debulked patients, positive associations were seen between intraepithelial cells expressing CD3, CD4, CD8, CD45RO, CD25, TIA-1, Granzyme B, FoxP3, CD20, and CD68, as well as expression of MHC class I and II by tumor cells. Disease-specific survival was positively associated with the markers CD8, CD3, FoxP3, TIA-1, CD20, MHC class I and class II. In other histological subtypes, immune infiltrates were less prevalent, and the only markers associated with survival were MHC class II (positive association in endometrioid cases) and myeloperoxidase (negative association in clear cell cases).Conclusions/SignificanceHost immune responses to EOC vary widely according to histological subtype and the extent of residual disease. TIA-1, FoxP3 and CD20 emerge as new positive prognostic factors in high-grade serous EOC from optimally debulked patients.
Highlights
Ovarian cancer is the most deadly gynecologic cancer, affecting more than 190,000 women worldwide each year (International Agency for Research on Cancer)
We found that 83.2% (163/196) of evaluable high-grade serous tumors were positive for intraepithelial CD3+ T cells, whereas CD4+ and CD8+ intraepithelial cells were found in 53.4% (103/193) and 84.0% (163/194) of evaluable tumors, respectively (Fig. 1A&B and data not shown)
We systematically examined the relationship between immune infiltrates and patient survival in three large epithelial ovarian cancer (EOC) series
Summary
Ovarian cancer is the most deadly gynecologic cancer, affecting more than 190,000 women worldwide each year (International Agency for Research on Cancer). Tumor-infiltrating CD3+ T cells are strongly associated with favorable prognosis, when CD3+ cells are localized within tumor epithelium [5,6,7,8,9]. These findings have been extended to the CD8+ T cell subset in particular [10,11,12,13,14,15,16,17], suggesting that cytotoxic T lymphocytes (CTLs) play an important role in the antitumor immune response. Tumor-infiltrating T cells are associated with survival in epithelial ovarian cancer (EOC), but their functional status is poorly understood, especially relative to the different risk categories and histological subtypes of EOC
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