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Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors.

Milne K, Köbel M, Kalloger SE, Barnes RO, Gao D, Gilks CB, Watson PH, Nelson BH - PLoS ONE (2009)

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Trev and Joyce Deeley Research Centre, BC Cancer Agency, Victoria, British Columbia, Canada.

ABSTRACT

Background: 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.

Methodology/principal findings: Tissue 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/significance: Host 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.

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Immunohistochemical analysis of high-grade serous EOC tumors showing (A,B) high and low expression of MHC class I, (C,D) high and low expression of MHC class II, and (E,F) high and low expression of COX-2.40X objective.
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pone-0006412-g002: Immunohistochemical analysis of high-grade serous EOC tumors showing (A,B) high and low expression of MHC class I, (C,D) high and low expression of MHC class II, and (E,F) high and low expression of COX-2.40X objective.

Mentions: We analyzed tumor cells for expression of MHC class I and II using a four-point scale (negative, focal [<10%], patchy [10-50%] or diffuse [>50%]). All evaluable tumors (185/185) expressed MHC class I to some degree (i.e., focal, patchy or diffuse), indicating they could theoretically present antigen to CD8+ T cells. For statistical analyses, only the highest category (diffuse, >50%) was considered positive (Fig. 2A&B). Using this threshold, 85.4% (158/185) of tumors were positive for MHC class I. MHC class I was positively associated with all three T cell subsets (CD3, CD4, and CD8), the activation markers CD45RO and CD25, and the differentiation markers TIA-1, Granzyme B and FoxP3 (Table 2).


Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors.

Milne K, Köbel M, Kalloger SE, Barnes RO, Gao D, Gilks CB, Watson PH, Nelson BH - PLoS ONE (2009)

Immunohistochemical analysis of high-grade serous EOC tumors showing (A,B) high and low expression of MHC class I, (C,D) high and low expression of MHC class II, and (E,F) high and low expression of COX-2.40X objective.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2712762&req=5

pone-0006412-g002: Immunohistochemical analysis of high-grade serous EOC tumors showing (A,B) high and low expression of MHC class I, (C,D) high and low expression of MHC class II, and (E,F) high and low expression of COX-2.40X objective.
Mentions: We analyzed tumor cells for expression of MHC class I and II using a four-point scale (negative, focal [<10%], patchy [10-50%] or diffuse [>50%]). All evaluable tumors (185/185) expressed MHC class I to some degree (i.e., focal, patchy or diffuse), indicating they could theoretically present antigen to CD8+ T cells. For statistical analyses, only the highest category (diffuse, >50%) was considered positive (Fig. 2A&B). Using this threshold, 85.4% (158/185) of tumors were positive for MHC class I. MHC class I was positively associated with all three T cell subsets (CD3, CD4, and CD8), the activation markers CD45RO and CD25, and the differentiation markers TIA-1, Granzyme B and FoxP3 (Table 2).

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Trev and Joyce Deeley Research Centre, BC Cancer Agency, Victoria, British Columbia, Canada.

ABSTRACT

Background: 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.

Methodology/principal findings: Tissue 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/significance: Host 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.

Show MeSH
Related in: MedlinePlus