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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

Immunohistochemical analysis of high-grade serous EOC tumors showing infiltrates expressing markers of T cell differentiation and activation.(A) CD4, (B) CD8, (C) CD45RO, (D) OX40, (E) CD25, (F) TIA-1, (G) Granzyme B, and (H) FoxP3. 40X objective.
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pone-0006412-g001: Immunohistochemical analysis of high-grade serous EOC tumors showing infiltrates expressing markers of T cell differentiation and activation.(A) CD4, (B) CD8, (C) CD45RO, (D) OX40, (E) CD25, (F) TIA-1, (G) Granzyme B, and (H) FoxP3. 40X objective.

Mentions: The tumors in this initial cohort had been previously assessed by immunohistochemistry (IHC) for a variety of lymphocyte markers, including CD3, CD4, CD8, CD20 and Granzyme B [12]. Intraepithelial lymphocytes (i.e., lymphocytes within the epithelial component of the tumor) were scored as either present (i.e. one or more intraepithelial lymphocytes present in at least one of two 0.6 mm cores) or absent. We re-analyzed this data focusing exclusively on high-grade serous cases. 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). CD4+ and CD8+ cellular infiltrates showed a strong positive association (p<0.0001). Table 2 shows statistical associations for these and all other markers studied in this initial cohort.


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 infiltrates expressing markers of T cell differentiation and activation.(A) CD4, (B) CD8, (C) CD45RO, (D) OX40, (E) CD25, (F) TIA-1, (G) Granzyme B, and (H) FoxP3. 40X objective.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0006412-g001: Immunohistochemical analysis of high-grade serous EOC tumors showing infiltrates expressing markers of T cell differentiation and activation.(A) CD4, (B) CD8, (C) CD45RO, (D) OX40, (E) CD25, (F) TIA-1, (G) Granzyme B, and (H) FoxP3. 40X objective.
Mentions: The tumors in this initial cohort had been previously assessed by immunohistochemistry (IHC) for a variety of lymphocyte markers, including CD3, CD4, CD8, CD20 and Granzyme B [12]. Intraepithelial lymphocytes (i.e., lymphocytes within the epithelial component of the tumor) were scored as either present (i.e. one or more intraepithelial lymphocytes present in at least one of two 0.6 mm cores) or absent. We re-analyzed this data focusing exclusively on high-grade serous cases. 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). CD4+ and CD8+ cellular infiltrates showed a strong positive association (p<0.0001). Table 2 shows statistical associations for these and all other markers studied in this initial cohort.

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