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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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Prevalence of immune infiltrates and other markers across different histologic subtypes of EOC.Bars indicate the percentage of tumors scoring positive for intrapithelial cells expressing CD3, CD8, CD4, CD45RO, CD25, FoxP3, TIA-1, Granzyme B, CD20 and CD68. Expression of MHC class I and II by tumor epithelium is also shown. Data were derived from optimally debulked patients.
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pone-0006412-g005: Prevalence of immune infiltrates and other markers across different histologic subtypes of EOC.Bars indicate the percentage of tumors scoring positive for intrapithelial cells expressing CD3, CD8, CD4, CD45RO, CD25, FoxP3, TIA-1, Granzyme B, CD20 and CD68. Expression of MHC class I and II by tumor epithelium is also shown. Data were derived from optimally debulked patients.

Mentions: In general, immune infiltrates were less prevalent in the other histological subtypes compared to the high-grade serous cases discussed previously. This was true for all lymphocyte markers studied (i.e., CD3, CD8, CD4, CD45RO, CD25, FoxP3, TIA-1, Granzyme B, and CD20) (Fig. 5). The difference was most striking for the markers FoxP3, CD25 and CD20. After the high-grade serous cases, the next highest frequency of immune infiltrates was seen in the endometrioid subtype (Fig. 5).


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)

Prevalence of immune infiltrates and other markers across different histologic subtypes of EOC.Bars indicate the percentage of tumors scoring positive for intrapithelial cells expressing CD3, CD8, CD4, CD45RO, CD25, FoxP3, TIA-1, Granzyme B, CD20 and CD68. Expression of MHC class I and II by tumor epithelium is also shown. Data were derived from optimally debulked patients.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0006412-g005: Prevalence of immune infiltrates and other markers across different histologic subtypes of EOC.Bars indicate the percentage of tumors scoring positive for intrapithelial cells expressing CD3, CD8, CD4, CD45RO, CD25, FoxP3, TIA-1, Granzyme B, CD20 and CD68. Expression of MHC class I and II by tumor epithelium is also shown. Data were derived from optimally debulked patients.
Mentions: In general, immune infiltrates were less prevalent in the other histological subtypes compared to the high-grade serous cases discussed previously. This was true for all lymphocyte markers studied (i.e., CD3, CD8, CD4, CD45RO, CD25, FoxP3, TIA-1, Granzyme B, and CD20) (Fig. 5). The difference was most striking for the markers FoxP3, CD25 and CD20. After the high-grade serous cases, the next highest frequency of immune infiltrates was seen in the endometrioid subtype (Fig. 5).

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