Skip to main content
Top
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

MPO density in primary cancer biopsies of ovarian carcinoma enhances the indicative value of IL-17 for chemosensitivity

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

Published in: BMC Cancer | Issue 1/2016

Login to get access

Abstract

Background

Cancer of the ovary is mostly discovered at a late stage and cannot be removed by surgery alone. Therefore surgery is usually followed by adjuvant chemotherapy. However, few reliable biomarkers exist to predict response to chemotherapy of ovarian cancer. Previously, we could demonstrate that IL-17 density is indicative for chemosensitivity. This study focuses on the predictive value of myeloperoxidase (MPO) concerning response to chemotherapy of ovarian cancer.

Methods

Biopsies of mostly high-grade primary serous ovarian carcinomas and their matched recurrences were stained with MPO after fixation in formalin and embedding in paraffin. For this staining the technique of tissue-microarray was used. Recurrence within 6 months of the completion of platinum-based chemotherapy was defined as chemoresistance as previously publised. Data for MPO could be analyzed in 92 biopsies.

Results

MPO and IL-17 positive immune cells correlated significantly in biopsies of primary and recurrent carcinomas (rs = 0.41; p = 0.004 and rs = 0.40; p = 0.007, respectively). MPO expression alone did not predict response to chemotherapy, but in multivariate cox regression analysis including age, residual disease, number of chemotherapy cycles, FIGO classification and combined categorized MPO and IL-17 cell densities of primary cancer biopsies, the combination of both immune markers was an independent prognostic factor for recurrence-free survival (p = 0.013, HR = .23, 95CI = 0.07–0.73). There was no chemoresistant patient in the subgroup of MPO + IL-17+, neither in primary nor in recurrent cancer biopsies.

Conclusions

High MPO positive cell density enhances the indicative value of IL-17 for response to chemotherapy in ovarian carcinoma. Although, these results have to be validated in a larger cohort.
Literature
1.
go back to reference Jemal A, Siegel R, Xu J, Ward E. Cancer statistics. CA Cancer J Clin. 2010;60(1542–4863 (Electronic)):277–300.CrossRefPubMed Jemal A, Siegel R, Xu J, Ward E. Cancer statistics. CA Cancer J Clin. 2010;60(1542–4863 (Electronic)):277–300.CrossRefPubMed
2.
go back to reference Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(1097–0215 (Electronic)):2893–917.CrossRefPubMed Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(1097–0215 (Electronic)):2893–917.CrossRefPubMed
3.
go back to reference Bray F, Loos AH, Tognazzo S, La Vecchia C. Ovarian cancer in Europe: cross-sectional trends in incidence and mortality in 28 countries, 1953–2000. Int J Cancer. 2005;113:977–90.CrossRefPubMed Bray F, Loos AH, Tognazzo S, La Vecchia C. Ovarian cancer in Europe: cross-sectional trends in incidence and mortality in 28 countries, 1953–2000. Int J Cancer. 2005;113:977–90.CrossRefPubMed
4.
go back to reference Liotta LA, Kohn EC. The microenvironment of the tumour-host interface. Nature. 2001;411(0028–0836 (Print)):375–9.CrossRefPubMed Liotta LA, Kohn EC. The microenvironment of the tumour-host interface. Nature. 2001;411(0028–0836 (Print)):375–9.CrossRefPubMed
5.
6.
go back to reference Uppaluri R, Dunn GP, Lewis Jr JS. Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in head and neck cancers. Cancer Immun. 2008;8(1424–9634 (Electronic)):16.PubMedPubMedCentral Uppaluri R, Dunn GP, Lewis Jr JS. Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in head and neck cancers. Cancer Immun. 2008;8(1424–9634 (Electronic)):16.PubMedPubMedCentral
7.
go back to reference Oble DA, Loewe R, Yu P, Mihm Jr MC. Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human melanoma. Cancer Immun. 2009;9(1424–9634 (Electronic)):3.PubMedPubMedCentral Oble DA, Loewe R, Yu P, Mihm Jr MC. Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human melanoma. Cancer Immun. 2009;9(1424–9634 (Electronic)):3.PubMedPubMedCentral
8.
go back to reference Nosho K, Baba Y, Tanaka N, Shima K, Hayashi M, Meyerhardt JA, Giovannucci E, Dranoff G, Fuchs CS, Ogino S. Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review. J Pathol. 2010;222(1096–9896 (Electronic)):350–66.CrossRefPubMedPubMedCentral Nosho K, Baba Y, Tanaka N, Shima K, Hayashi M, Meyerhardt JA, Giovannucci E, Dranoff G, Fuchs CS, Ogino S. Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review. J Pathol. 2010;222(1096–9896 (Electronic)):350–66.CrossRefPubMedPubMedCentral
9.
go back to reference Takagi S, Chen K, Schwarz R, Iwatsuki S, Herberman RB, Whiteside TL. Functional and phenotypic analysis of tumor-infiltrating lymphocytes isolated from human primary and metastatic liver tumors and cultured in recombinant interleukin-2 22. Cancer. 1989;63(0008–543X (Print)):102–11.CrossRefPubMed Takagi S, Chen K, Schwarz R, Iwatsuki S, Herberman RB, Whiteside TL. Functional and phenotypic analysis of tumor-infiltrating lymphocytes isolated from human primary and metastatic liver tumors and cultured in recombinant interleukin-2 22. Cancer. 1989;63(0008–543X (Print)):102–11.CrossRefPubMed
10.
go back to reference Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoue F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pages F. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(1095–9203 (Electronic)):1960–4.CrossRefPubMed Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoue F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pages F. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(1095–9203 (Electronic)):1960–4.CrossRefPubMed
11.
go back to reference Su X, Ye J, Hsueh EC, Zhang Y, Hoft DF, Peng G. Tumor microenvironments direct the recruitment and expansion of human Th17 cells. J Immunol. 2010;184(1550–6606 (Electronic)):1630–41.CrossRefPubMed Su X, Ye J, Hsueh EC, Zhang Y, Hoft DF, Peng G. Tumor microenvironments direct the recruitment and expansion of human Th17 cells. J Immunol. 2010;184(1550–6606 (Electronic)):1630–41.CrossRefPubMed
12.
go back to reference Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12(1474–1768 (Electronic)):298–306.CrossRefPubMed Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12(1474–1768 (Electronic)):298–306.CrossRefPubMed
13.
go back to reference Grizzi F, Bianchi P, Malesci A, Laghi L. Prognostic value of innate and adaptive immunity in colorectal cancer. World J Gastroenterol. 2013;19:174–84.CrossRefPubMedPubMedCentral Grizzi F, Bianchi P, Malesci A, Laghi L. Prognostic value of innate and adaptive immunity in colorectal cancer. World J Gastroenterol. 2013;19:174–84.CrossRefPubMedPubMedCentral
14.
go back to reference Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T, Bruneval P, Trajanoski Z, Fridman W-H, Pages F, Galon J. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol. 2011;29:610–8.CrossRefPubMed Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T, Bruneval P, Trajanoski Z, Fridman W-H, Pages F, Galon J. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol. 2011;29:610–8.CrossRefPubMed
15.
go back to reference He Z, Gao J, Wang Q, Liu M, Li Y, Li X, Tang H, Zheng J. S100P contributes to chemosensitivity of human ovarian cancer cell line OVCAR3. Oncol Rep. 2008;20:325–32.PubMed He Z, Gao J, Wang Q, Liu M, Li Y, Li X, Tang H, Zheng J. S100P contributes to chemosensitivity of human ovarian cancer cell line OVCAR3. Oncol Rep. 2008;20:325–32.PubMed
16.
go back to reference Sato S, Kigawa J, Minagawa Y, Okada M, Shimada M, Takahashi M, Kamazawa S, Terakawa N. Chemosensitivity and p53-dependent apoptosis in epithelial ovarian carcinoma. Cancer. 1999;86:1307–13.CrossRefPubMed Sato S, Kigawa J, Minagawa Y, Okada M, Shimada M, Takahashi M, Kamazawa S, Terakawa N. Chemosensitivity and p53-dependent apoptosis in epithelial ovarian carcinoma. Cancer. 1999;86:1307–13.CrossRefPubMed
17.
go back to reference Polcher M, Braun M, Friedrichs N, Rudlowski C, Bercht E, Fimmers R, Sauerwald A, Keyver-Paik M-D, Kubler K, Buttner R, Kuhn WC, Hernando J-J. Foxp3(+) cell infiltration and granzyme B(+)/Foxp3(+) cell ratio are associated with outcome in neoadjuvant chemotherapy-treated ovarian carcinoma. Cancer Immunol Immunother. 2010;59:909–19.CrossRefPubMed Polcher M, Braun M, Friedrichs N, Rudlowski C, Bercht E, Fimmers R, Sauerwald A, Keyver-Paik M-D, Kubler K, Buttner R, Kuhn WC, Hernando J-J. Foxp3(+) cell infiltration and granzyme B(+)/Foxp3(+) cell ratio are associated with outcome in neoadjuvant chemotherapy-treated ovarian carcinoma. Cancer Immunol Immunother. 2010;59:909–19.CrossRefPubMed
18.
go back to reference Wolf D, Wolf AM, Rumpold H, Fiegl H, Zeimet AG, Muller-Holzner E, Deibl M, Gastl G, Gunsilius E, Marth C. The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res. 2005;11:8326–31.CrossRefPubMed Wolf D, Wolf AM, Rumpold H, Fiegl H, Zeimet AG, Muller-Holzner E, Deibl M, Gastl G, Gunsilius E, Marth C. The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res. 2005;11:8326–31.CrossRefPubMed
19.
go back to reference Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival 39. Nat Med. 2004;10(1078–8956 (Print)):942–9.CrossRefPubMed Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival 39. Nat Med. 2004;10(1078–8956 (Print)):942–9.CrossRefPubMed
20.
go back to reference Di Carlo E, Forni G, Lollini P, Colombo MP, Modesti A, Musiani P. The intriguing role of polymorphonuclear neutrophils in antitumor reactions. Blood. 2001;97:339–45.CrossRefPubMed Di Carlo E, Forni G, Lollini P, Colombo MP, Modesti A, Musiani P. The intriguing role of polymorphonuclear neutrophils in antitumor reactions. Blood. 2001;97:339–45.CrossRefPubMed
21.
go back to reference Granot Z, Henke E, Comen EA, King TA, Norton L, Benezra R. Tumor entrained neutrophils inhibit seeding in the premetastatic lung. Cancer Cell. 2011;20:300–14.CrossRefPubMedPubMedCentral Granot Z, Henke E, Comen EA, King TA, Norton L, Benezra R. Tumor entrained neutrophils inhibit seeding in the premetastatic lung. Cancer Cell. 2011;20:300–14.CrossRefPubMedPubMedCentral
22.
go back to reference Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, Worthen GS, Albelda SM. Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell. 2009;16:183–94.CrossRefPubMedPubMedCentral Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, Worthen GS, Albelda SM. Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell. 2009;16:183–94.CrossRefPubMedPubMedCentral
23.
go back to reference Jablonska J, Leschner S, Westphal K, Lienenklaus S, Weiss S. Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model. J Clin Invest. 2010;120:1151–64.CrossRefPubMedPubMedCentral Jablonska J, Leschner S, Westphal K, Lienenklaus S, Weiss S. Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model. J Clin Invest. 2010;120:1151–64.CrossRefPubMedPubMedCentral
24.
go back to reference Fridlender ZG, Albelda SM. Tumor-associated neutrophils: friend or foe? Carcinogenesis. 2012;33:949–55.CrossRefPubMed Fridlender ZG, Albelda SM. Tumor-associated neutrophils: friend or foe? Carcinogenesis. 2012;33:949–55.CrossRefPubMed
25.
26.
go back to reference Mantovani A, Cassatella MA, Costantini C, Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 2011;11:519–31.CrossRefPubMed Mantovani A, Cassatella MA, Costantini C, Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 2011;11:519–31.CrossRefPubMed
27.
go back to reference Droeser RA, Guth U, Eppenberger-Castori S, Stadlmann S, Hirt C, Terracciano L, Singer G. High IL-17-positive tumor immune cell infiltration is indicative for chemosensitivity of ovarian carcinoma. J Cancer Res Clin Oncol. 2013;139(1432–1335 (Electronic)):1295–302.CrossRefPubMed Droeser RA, Guth U, Eppenberger-Castori S, Stadlmann S, Hirt C, Terracciano L, Singer G. High IL-17-positive tumor immune cell infiltration is indicative for chemosensitivity of ovarian carcinoma. J Cancer Res Clin Oncol. 2013;139(1432–1335 (Electronic)):1295–302.CrossRefPubMed
28.
go back to reference Li L, Huang L, Vergis AL, Ye H, Bajwa A, Narayan V, Strieter RM, Rosin DL, Okusa MD. IL-17 produced by neutrophils regulates IFN-gamma-mediated neutrophil migration in mouse kidney ischemia-reperfusion injury. J Clin Invest. 2010;120:331–42.CrossRefPubMed Li L, Huang L, Vergis AL, Ye H, Bajwa A, Narayan V, Strieter RM, Rosin DL, Okusa MD. IL-17 produced by neutrophils regulates IFN-gamma-mediated neutrophil migration in mouse kidney ischemia-reperfusion injury. J Clin Invest. 2010;120:331–42.CrossRefPubMed
29.
go back to reference Lin AM, Rubin CJ, Khandpur R, Wang JY, Riblett M, Yalavarthi S, Villanueva EC, Shah P, Kaplan MJ, Bruce AT. Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. J Immunol. 2011;187:490–500.CrossRefPubMedPubMedCentral Lin AM, Rubin CJ, Khandpur R, Wang JY, Riblett M, Yalavarthi S, Villanueva EC, Shah P, Kaplan MJ, Bruce AT. Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. J Immunol. 2011;187:490–500.CrossRefPubMedPubMedCentral
30.
go back to reference Cua DJ, Tato CM. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol. 2010;10:479–89.CrossRefPubMed Cua DJ, Tato CM. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol. 2010;10:479–89.CrossRefPubMed
31.
go back to reference Eruslanov EB, Bhojnagarwala PS, Quatromoni JG, Stephen TL, Ranganathan A, Deshpande C, Akimova T, Vachani A, Litzky L, Hancock WW, Conejo-Garcia JR, Feldman M, Albelda SM, Singhal S. Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer. J Clin Invest. 2014;124:5466–80.CrossRefPubMedPubMedCentral Eruslanov EB, Bhojnagarwala PS, Quatromoni JG, Stephen TL, Ranganathan A, Deshpande C, Akimova T, Vachani A, Litzky L, Hancock WW, Conejo-Garcia JR, Feldman M, Albelda SM, Singhal S. Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer. J Clin Invest. 2014;124:5466–80.CrossRefPubMedPubMedCentral
32.
go back to reference Krawisz JE, Sharon P, Stenson WF. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology. 1984;87:1344–50.PubMed Krawisz JE, Sharon P, Stenson WF. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology. 1984;87:1344–50.PubMed
33.
go back to reference Heinecke JW, Li W, Francis GA, Goldstein JA. Tyrosyl radical generated by myeloperoxidase catalyzes the oxidative cross-linking of proteins. J Clin Invest. 1993;91:2866–72.CrossRefPubMedPubMedCentral Heinecke JW, Li W, Francis GA, Goldstein JA. Tyrosyl radical generated by myeloperoxidase catalyzes the oxidative cross-linking of proteins. J Clin Invest. 1993;91:2866–72.CrossRefPubMedPubMedCentral
34.
go back to reference Kanayama A, Miyamoto Y. Apoptosis triggered by phagocytosis-related oxidative stress through FLIPS down-regulation and JNK activation. J Leukoc Biol. 2007;82:1344–52.CrossRefPubMed Kanayama A, Miyamoto Y. Apoptosis triggered by phagocytosis-related oxidative stress through FLIPS down-regulation and JNK activation. J Leukoc Biol. 2007;82:1344–52.CrossRefPubMed
35.
go back to reference Stadlmann S, Dirnhofer S, Guth U, Thies S, Singer G. ERCC1-immunoexpression does not predict platinum-resistance in ovarian cancer. Gynecol Oncol. 2008;108(1)252–3.CrossRefPubMed Stadlmann S, Dirnhofer S, Guth U, Thies S, Singer G. ERCC1-immunoexpression does not predict platinum-resistance in ovarian cancer. Gynecol Oncol. 2008;108(1)252–3.CrossRefPubMed
36.
go back to reference Stadlmann S, Gueth U, Baumhoer D, Moch H, Terracciano L, Singer G. Glypican-3 expression in primary and recurrent ovarian carcinomas. Int J Gynecol Pathol. 2007;26:341–4.CrossRefPubMed Stadlmann S, Gueth U, Baumhoer D, Moch H, Terracciano L, Singer G. Glypican-3 expression in primary and recurrent ovarian carcinomas. Int J Gynecol Pathol. 2007;26:341–4.CrossRefPubMed
37.
go back to reference Stadlmann S, Gueth U, Wight E, Kunz-Schughart LA, Hartmann A, Singer G. Expression of peroxisome proliferator activated receptor gamma and cyclo-oxygenase 2 in primary and recurrent ovarian carcinoma. J Clin Pathol. 2007;60:307–10.CrossRefPubMed Stadlmann S, Gueth U, Wight E, Kunz-Schughart LA, Hartmann A, Singer G. Expression of peroxisome proliferator activated receptor gamma and cyclo-oxygenase 2 in primary and recurrent ovarian carcinoma. J Clin Pathol. 2007;60:307–10.CrossRefPubMed
38.
go back to reference Stadlmann S, Gueth U, Reiser U, Diener P-A, Zeimet AG, Wight E, Mirlacher M, Sauter G, Mihatsch MJ, Singer G. Epithelial growth factor receptor status in primary and recurrent ovarian cancer. Mod Pathol. 2006;19:607–10.CrossRefPubMed Stadlmann S, Gueth U, Reiser U, Diener P-A, Zeimet AG, Wight E, Mirlacher M, Sauter G, Mihatsch MJ, Singer G. Epithelial growth factor receptor status in primary and recurrent ovarian cancer. Mod Pathol. 2006;19:607–10.CrossRefPubMed
39.
40.
go back to reference Singer G, Oldt 3rd R, Cohen Y, Wang BG, Sidransky D, Kurman RJ, Shih I-M. Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J Natl Cancer Inst. 2003;95:484–6.CrossRefPubMed Singer G, Oldt 3rd R, Cohen Y, Wang BG, Sidransky D, Kurman RJ, Shih I-M. Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J Natl Cancer Inst. 2003;95:484–6.CrossRefPubMed
41.
go back to reference Jazaeri AA, Awtrey CS, Chandramouli GVR, Chuang YE, Khan J, Sotiriou C, Aprelikova O, Yee CJ, Zorn KK, Birrer MJ, Barrett JC, Boyd J. Gene expression profiles associated with response to chemotherapy in epithelial ovarian cancers. Clin Cancer Res. 2005;11:6300–10.CrossRefPubMed Jazaeri AA, Awtrey CS, Chandramouli GVR, Chuang YE, Khan J, Sotiriou C, Aprelikova O, Yee CJ, Zorn KK, Birrer MJ, Barrett JC, Boyd J. Gene expression profiles associated with response to chemotherapy in epithelial ovarian cancers. Clin Cancer Res. 2005;11:6300–10.CrossRefPubMed
42.
go back to reference Sauter G, Simon R, Hillan K. Tissue microarrays in drug discovery. Nat Rev Drug Discov. 2003;2(1474–1776 (Print)):962–72.CrossRefPubMed Sauter G, Simon R, Hillan K. Tissue microarrays in drug discovery. Nat Rev Drug Discov. 2003;2(1474–1776 (Print)):962–72.CrossRefPubMed
43.
go back to reference Zlobec I, Steele R, Terracciano L, Jass JR, Lugli A. Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer. J Clin Pathol. 2007;60(0021–9746 (Print)):1112–6.CrossRefPubMed Zlobec I, Steele R, Terracciano L, Jass JR, Lugli A. Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer. J Clin Pathol. 2007;60(0021–9746 (Print)):1112–6.CrossRefPubMed
44.
go back to reference Stoppacciaro A, Melani C, Parenza M, Mastracchio A, Bassi C, Baroni C, Parmiani G, Colombo MP. Regression of an established tumor genetically modified to release granulocyte colony-stimulating factor requires granulocyte-T cell cooperation and T cell-produced interferon gamma. J Exp Med. 1993;178:151–61.CrossRefPubMed Stoppacciaro A, Melani C, Parenza M, Mastracchio A, Bassi C, Baroni C, Parmiani G, Colombo MP. Regression of an established tumor genetically modified to release granulocyte colony-stimulating factor requires granulocyte-T cell cooperation and T cell-produced interferon gamma. J Exp Med. 1993;178:151–61.CrossRefPubMed
45.
go back to reference Colombo MP, Ferrari G, Stoppacciaro A, Parenza M, Rodolfo M, Mavilio F, Parmiani G. Granulocyte colony-stimulating factor gene transfer suppresses tumorigenicity of a murine adenocarcinoma in vivo. J Exp Med. 1991;173:889–97.CrossRefPubMed Colombo MP, Ferrari G, Stoppacciaro A, Parenza M, Rodolfo M, Mavilio F, Parmiani G. Granulocyte colony-stimulating factor gene transfer suppresses tumorigenicity of a murine adenocarcinoma in vivo. J Exp Med. 1991;173:889–97.CrossRefPubMed
46.
go back to reference Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348:203–13.CrossRefPubMed Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348:203–13.CrossRefPubMed
47.
go back to reference Kryczek I, Banerjee M, Cheng P, Vatan L, Szeliga W, Wei S, Huang E, Finlayson E, Simeone D, Welling TH, Chang A, Coukos G, Liu R, Zou W. Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood. 2009;114(1528–0020 (Electronic)):1141–9.CrossRefPubMedPubMedCentral Kryczek I, Banerjee M, Cheng P, Vatan L, Szeliga W, Wei S, Huang E, Finlayson E, Simeone D, Welling TH, Chang A, Coukos G, Liu R, Zou W. Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood. 2009;114(1528–0020 (Electronic)):1141–9.CrossRefPubMedPubMedCentral
48.
go back to reference Charles KA, Kulbe H, Soper R, Escorcio-Correia M, Lawrence T, Schultheis A, Chakravarty P, Thompson RG, Kollias G, Smyth JF, Balkwill FR, Hagemann T. The tumor-promoting actions of TNF-alpha involve TNFR1 and IL-17 in ovarian cancer in mice and humans. J Clin Invest. 2009;119:3011–23.CrossRefPubMedPubMedCentral Charles KA, Kulbe H, Soper R, Escorcio-Correia M, Lawrence T, Schultheis A, Chakravarty P, Thompson RG, Kollias G, Smyth JF, Balkwill FR, Hagemann T. The tumor-promoting actions of TNF-alpha involve TNFR1 and IL-17 in ovarian cancer in mice and humans. J Clin Invest. 2009;119:3011–23.CrossRefPubMedPubMedCentral
Metadata
Title
MPO density in primary cancer biopsies of ovarian carcinoma enhances the indicative value of IL-17 for chemosensitivity
Authors
Raoul A. Droeser
Robert Mechera
Silvio Däster
Benjamin Weixler
Marko Kraljević
Tarik Delko
Uwe Güth
Sylvia Stadlmann
Luigi Terracciano
Gad Singer
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2673-7

Other articles of this Issue 1/2016

BMC Cancer 1/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine