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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

High OX40 expression in recurrent ovarian carcinoma is indicative for response to repeated chemotherapy

Authors: Michaela Ramser, Simone Eichelberger, Silvio Däster, Benjamin Weixler, Marko Kraljević, Robert Mechera, Athanasios Tampakis, Tarik Delko, Uwe Güth, Sylvia Stadlmann, Luigi Terracciano, Raoul A. Droeser, Gad Singer

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Ovarian carcinoma (OC) is the fifth most common female cancer and mostly diagnosed at an advanced stage. Surgical debulking is usually followed by adjuvant platinum-based chemotherapy. Only few biomarkers are known to be related to chemosensitivity. OX40 is a TNF receptor member and expressed on activated CD4+ and CD8+ T cells. It is known that OX40 signaling promotes survival and responds to various immune cells of the innate and adaptive immune system. Therefore we investigated the indicative value of OX40 expression for recurrence and survival in OC.

Methods

A tissue microarray of biopsies of mostly high-grade primary serous OC and matched recurrences of 47 patients was stained with OX40. Recurrence within 6 months of the completion of platinum-based chemotherapy was defined as chemoresistance.

Results

Chemosensitivity correlated significantly with high OX40 positive immune cell density in primary cancer biopsies (p = 0.027). Furthermore patients with a higher OX40 expression in recurrent cancer biopsies showed a better outcome in recurrence free survival (RFS) (p = 0.017) and high OX40 expression was associated with chemosensitivity (p = 0.008). OX40 positive TICI in recurrent carcinomas significantly correlated with IL-17 positive tumor infiltrating immune cells in primary carcinomas (r s  = 0.34; p = 0.023). Univariate cox regression analysis revealed a significant longer RFS and higher numbers of chemotherapy cycles for high OX40 tumor cell expression in recurrent cancer biopsies (HR 0.39, 95%CI 0.16–0.94, p = 0.036 and 1.28, 95%CI 1.05–1.55; p = 0.013).

Conclusion

High OX40 expression in OC is correlated with chemosensitivity and improved RFS in OC. Patients might therefore benefit from a second line therapy.
Literature
1.
Ferlay J, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–917.CrossRefPubMed
2.
Bray F, et al. Ovarian cancer in Europe: cross-sectional trends in incidence and mortality in 28 countries, 1953-2000. Int J Cancer. 2005;113(6):977–90.CrossRefPubMed
3.
4.
5.
Coburn SB, et al. International patterns and trends in ovarian cancer incidence, overall and by histologic subtype. Int J Cancer. 2017;140(11):2451–60.
6.
He Z, et al. S100P contributes to chemosensitivity of human ovarian cancer cell line OVCAR3. Oncol Rep. 2008;20(2):325–32.PubMed
7.
Sato S, et al. Chemosensitivity and p53-dependent apoptosis in epithelial ovarian carcinoma. Cancer. 1999;86(7):1307–13.CrossRefPubMed
8.
Polcher M, et al. Foxp3(+) cell infiltration and granzyme B (+)/Foxp3 (+) cell ratio are associated with outcome in neoadjuvant chemotherapy-treated ovarian carcinoma. Cancer Immunol Immunother. 2010;59(6):909–19.CrossRefPubMed
9.
Fridman WH, et al. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12(4):298–306.CrossRefPubMed
10.
Zhang L, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348(3):203–13.CrossRefPubMed
11.
Halama N, et al. Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy. Cancer Res. 2011;71(17):5670–7.CrossRefPubMed
12.
13.
14.
15.
16.
17.
Sugamura K, Ishii N, Weinberg AD. Therapeutic targeting of the effector T-cell co-stimulatory molecule OX40. Nat Rev Immunol. 2004;4(6):420–31.CrossRefPubMed
18.
Weinberg AD, et al. The generation of T cell memory: a review describing the molecular and cellular events following OX40 (CD134) engagement. J Leukoc Biol. 2004;75(6):962–72.CrossRefPubMed
19.
Bansal-Pakala P, et al. Costimulation of CD8 T cell responses by OX40. J Immunol. 2004;172(8):4821–5.CrossRefPubMed
20.
De Smedt T, et al. Ox40 costimulation enhances the development of T cell responses induced by dendritic cells in vivo. J Immunol. 2002;168(2):661–70.CrossRefPubMed
21.
Maxwell JR, et al. Danger and OX40 receptor signaling synergize to enhance memory T cell survival by inhibiting peripheral deletion. J Immunol. 2000;164(1):107–12.CrossRefPubMed
22.
Soroosh P, et al. Differential requirements for OX40 signals on generation of effector and central memory CD4+ T cells. J Immunol. 2007;179(8):5014–23.CrossRefPubMed
23.
Gough MJ, et al. OX40 agonist therapy enhances CD8 infiltration and decreases immune suppression in the tumor. Cancer Res. 2008;68(13):5206–15.CrossRefPubMed
24.
25.
Droeser RA, et al. High IL-17-positive tumor immune cell infiltration is indicative for chemosensitivity of ovarian carcinoma. J Cancer Res Clin Oncol. 2013;139(8):1295–302.CrossRefPubMed
26.
Li L, et al. IL-17 produced by neutrophils regulates IFN-gamma-mediated neutrophil migration in mouse kidney ischemia-reperfusion injury. J Clin Invest. 2010;120(1):331–42.CrossRefPubMed
27.
28.
Cua DJ, Tato CM. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol. 2010;10(7):479–89.CrossRefPubMed
29.
Droeser RA, et al. MPO density in primary cancer biopsies of ovarian carcinoma enhances the indicative value of IL-17 for chemosensitivity. BMC Cancer. 2016;16:639.CrossRefPubMedPubMedCentral
30.
Peng J, et al. Chemotherapy induces programmed cell death-ligand 1 overexpression via the nuclear factor-kappaB to Foster an immunosuppressive tumor microenvironment in ovarian Cancer. Cancer Res. 2015;75(23):5034–45.CrossRefPubMed
31.
32.
Singer G, et al. Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J Natl Cancer Inst. 2003;95(6):484–6.CrossRefPubMed
33.
Jazaeri AA, et al. Gene expression profiles associated with response to chemotherapy in epithelial ovarian cancers. Clin Cancer Res. 2005;11(17):6300–10.CrossRefPubMed
34.
Stadlmann S, et al. ERCC1-immunoexpression does not predict platinum-resistance in ovarian cancer. Gynecol Oncol. 2008;108(1):252–3.CrossRefPubMed
35.
Stadlmann S, et al. Glypican-3 expression in primary and recurrent ovarian carcinomas. Int J Gynecol Pathol. 2007;26(3):341–4.CrossRefPubMed
36.
Stadlmann S, et al. Expression of peroxisome proliferator activated receptor gamma and cyclo-oxygenase 2 in primary and recurrent ovarian carcinoma. J Clin Pathol. 2007;60(3):307–10.CrossRefPubMed
37.
Stadlmann S, et al. Epithelial growth factor receptor status in primary and recurrent ovarian cancer. Mod Pathol. 2006;19(4):607–10.CrossRefPubMed
38.
Sauter G, Simon R, Hillan K. Tissue microarrays in drug discovery. Nat Rev Drug Discov. 2003;2(12):962–72.CrossRefPubMed
39.
Zlobec I, et al. Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer. J Clin Pathol. 2007;60(10):1112–6.CrossRefPubMed
40.
Ledermann JA, et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2013;24(suppl_6):vi24–32.PubMed
41.
42.
Leffers N, et al. Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer. Cancer Immunol Immunother. 2008;58(3):449.CrossRefPubMed
Metadata
Title
High OX40 expression in recurrent ovarian carcinoma is indicative for response to repeated chemotherapy
Authors
Michaela Ramser
Simone Eichelberger
Silvio Däster
Benjamin Weixler
Marko Kraljević
Robert Mechera
Athanasios Tampakis
Tarik Delko
Uwe Güth
Sylvia Stadlmann
Luigi Terracciano
Raoul A. Droeser
Gad Singer
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4339-0

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