Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Jul 29;4(7):e6412.
doi: 10.1371/journal.pone.0006412.

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

Katy Milne  1 , Martin Köbel, Steven E Kalloger, Rebecca O Barnes, Dongxia Gao, C Blake Gilks, Peter H Watson, Brad H Nelson
Affiliations

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

Katy Milne et al. PLoS One. .

Erratum in

  • PLoS One. 2013;8(7). doi:10.1371/annotation/976c923b-d991-4a33-b060-cdd8770bdf5d

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.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. 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.
Figure 2
Figure 2. 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.
Figure 3
Figure 3. Immunohistochemical analysis of high-grade serous EOC tumors showing infiltrates expressing (A) CD20 (B cells), (B) CD1a (immature DCs), (C) Myeloperoxidase (granulocytes), and (D) CD68 (macrophages).
40X objective.
Figure 4
Figure 4. 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.
Figure 5
Figure 5. 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.
See this image and copyright information in PMC

References

    1. Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2003;21:3194–3200. - PubMed
    1. du Bois A, Luck HJ, Meier W, Adams HP, Mobus V, et al. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst. 2003;95:1320–1329. - PubMed
    1. Holschneider CH, Berek JS. Ovarian cancer: epidemiology, biology, and prognostic factors. Semin Surg Oncol. 2000;19:3–10. - PubMed
    1. Ozols RF. Management of advanced ovarian cancer consensus summary. Advanced Ovarian Cancer Consensus Faculty. Semin Oncol. 2000;27:47–49. - PubMed
    1. Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348:203–213. - PubMed

Publication types