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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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Related in: MedlinePlus

Immune infiltrates and survival in ovarian cancer.Kaplan-Meier curves showing disease-specific survival for patients scored as positive or negative for (A) CD3, (B) CD8, (C) CD4, (D) FoxP3, (E) CD20, (F) CD68, (G) TIA-1, (H) Granzyme B, (I) MHC Class I and (J) MHC Class II. Data were derived from optimally debulked patients with high-grade serous EOC.
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pone-0006412-g004: Immune infiltrates and survival in ovarian cancer.Kaplan-Meier curves showing disease-specific survival for patients scored as positive or negative for (A) CD3, (B) CD8, (C) CD4, (D) FoxP3, (E) CD20, (F) CD68, (G) TIA-1, (H) Granzyme B, (I) MHC Class I and (J) MHC Class II. Data were derived from optimally debulked patients with high-grade serous EOC.

Mentions: Kaplan-Meier analysis was performed to assess the association between various immune infiltrates and disease-specific survival (DSS). Consistent with prior reports [5]-[7], [10]-[17], intraepithelial CD3+ and CD8+ cells were associated with increased DSS (p = 0.0009 and 0.0008 respectively) (Fig. 4A&B). Intraepithelial CD4+ cells showed a trend towards increased DSS, but this was not statistically significant (Fig. 4C). The NK cell markers CD56 and CD57 showed no association with DSS (data not shown).


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)

Immune infiltrates and survival in ovarian cancer.Kaplan-Meier curves showing disease-specific survival for patients scored as positive or negative for (A) CD3, (B) CD8, (C) CD4, (D) FoxP3, (E) CD20, (F) CD68, (G) TIA-1, (H) Granzyme B, (I) MHC Class I and (J) MHC Class II. Data were derived from optimally debulked patients with high-grade serous EOC.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0006412-g004: Immune infiltrates and survival in ovarian cancer.Kaplan-Meier curves showing disease-specific survival for patients scored as positive or negative for (A) CD3, (B) CD8, (C) CD4, (D) FoxP3, (E) CD20, (F) CD68, (G) TIA-1, (H) Granzyme B, (I) MHC Class I and (J) MHC Class II. Data were derived from optimally debulked patients with high-grade serous EOC.
Mentions: Kaplan-Meier analysis was performed to assess the association between various immune infiltrates and disease-specific survival (DSS). Consistent with prior reports [5]-[7], [10]-[17], intraepithelial CD3+ and CD8+ cells were associated with increased DSS (p = 0.0009 and 0.0008 respectively) (Fig. 4A&B). Intraepithelial CD4+ cells showed a trend towards increased DSS, but this was not statistically significant (Fig. 4C). The NK cell markers CD56 and CD57 showed no association with DSS (data not shown).

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