High IL-17-positive tumor immune cell infiltration is indicative for chemosensitivity of ovarian carcinoma

被引:22
作者
Droeser, Raoul A. [1 ,2 ]
Gueth, Uwe [3 ,4 ]
Eppenberger-Castori, Serenella [5 ]
Stadlmann, Sylvia [6 ]
Hirt, Christian [1 ,2 ]
Terracciano, Luigi [5 ]
Singer, Gad [6 ]
机构
[1] Univ Basel Hosp, Dept Surg, CH-4031 Basel, Switzerland
[2] Inst Surg Res & Hosp Management ICFS, CH-4031 Basel, Switzerland
[3] Univ Basel Hosp, Dept Gynecol & Obstet, CH-4031 Basel, Switzerland
[4] Kantonsspital Winterthur, Dept Gynecol & Obstet, CH-8400 Winterthur, Switzerland
[5] Univ Basel Hosp, Inst Pathol, CH-4031 Basel, Switzerland
[6] Kantonsspital Baden AG, Inst Pathol, CH-5404 Baden, Switzerland
关键词
Forkhead box P3; Tissue microarray; Regulatory T cell; Interleukin-17; Chemosensitivity; Ovarian cancer; REGULATORY T-CELLS; EXPRESSION; CANCER; CHEMOTHERAPY; RECRUITMENT; PROGNOSIS; SURVIVAL;
D O I
10.1007/s00432-013-1441-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Ovarian carcinoma in most instances is diagnosed in an advanced stage which cannot be cured by surgical tumor debulking alone. Standard adjuvant chemotherapy usually follows surgical procedures. Yet, few reliable predictive tissue markers exist for the response of ovarian carcinoma to chemotherapy. In this study, we evaluated the predictive value of IL-17- and FOXP3-positive tumor immune cell infiltration (TICI) for response to chemotherapy in ovarian carcinoma. Formalin fixed and paraffin embedded biopsies of mostly high-grade primary serous ovarian carcinomas and their matched recurrences were immunostained with IL-17 and FOXP3 on a tissue microarray. Chemoresistance was defined as tumor recurrence within 6 months of the completion of platinum-based chemotherapy. In 94 and 90 biopsies, conclusive data for IL-17 and FOXP3 were available, respectively. IL-17, but not FOXP3-positive TICI, displayed a significantly higher density in biopsies of chemosensitive tumors (p = 0.01). No significant difference in the expression of IL-17 and FOXP3 TICI was observed in all paired primary and recurrent biopsies without respect to chemoresponse (p = 0.77 and p = 0.87, respectively). However, significantly more IL-17-positive recurrences were encountered in the group of patients with chemosensitive tumors (p = 0.008). High IL-17-positive TICI is indicative for response to chemotherapy in ovarian carcinoma. Higher frequency of IL-17-positive TICI might persist in recurrent tumor tissues of chemosensitive biopsies, suggesting repetitive platinum-based chemotherapy as an appropriate therapy for patients with IL-17-positive recurrences.
引用
收藏
页码:1295 / 1302
页数:8
相关论文
共 44 条
[1]  
[Anonymous], J IMMUNOL
[2]   Hypoxia controls CD4+CD25+ regulatory T-cell homeostasis via hypoxia-inducible factor-1α [J].
Ben-Shoshan, Jeremy ;
Maysel-Auslender, Sophia ;
Mor, Adi ;
Keren, Gad ;
George, Jacob .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2008, 38 (09) :2412-2418
[3]   Induction and effector functions of TH17 cells [J].
Bettelli, Estelle ;
Korn, Thomas ;
Oukka, Mohamed ;
Kuchroo, Vijay K. .
NATURE, 2008, 453 (7198) :1051-1057
[4]   The tumor-promoting actions of TNF-α involve TNFR1 and IL-17 in ovarian cancer in mice and humans [J].
Charles, Kellie A. ;
Kulbe, Hagen ;
Soper, Robin ;
Escorcio-Correia, Monica ;
Lawrence, Toby ;
Schultheis, Anne ;
Chakravarty, Probir ;
Thompson, Richard G. ;
Kollias, George ;
Smyth, John F. ;
Balkwill, Frances R. ;
Hagemann, Thorsten .
JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (10) :3011-3023
[5]   Innate IL-17-producing cells: the sentinels of the immune system [J].
Cua, Daniel J. ;
Tato, Cristina M. .
NATURE REVIEWS IMMUNOLOGY, 2010, 10 (07) :479-489
[6]   Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival [J].
Curiel, TJ ;
Coukos, G ;
Zou, LH ;
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, LP ;
Zou, WP .
NATURE MEDICINE, 2004, 10 (09) :942-949
[7]   The Predictive Value of HLA Class I Tumor Cell Expression and Presence of Intratumoral Tregs for Chemotherapy in Patients with Early Breast Cancer [J].
de Kruijf, Esther M. ;
van Nes, Johanna G. H. ;
Sajet, Anita ;
Tummers, Quirijn R. J. G. ;
Putter, Hein ;
Osanto, Susanne ;
Speetjens, Frank M. ;
Smit, Vincent T. H. B. M. ;
Liefers, Gerrit Jan ;
van de Velde, Cornelis J. H. ;
Kuppen, Peter J. K. .
CLINICAL CANCER RESEARCH, 2010, 16 (04) :1272-1280
[8]   The prognostic value of the hypoxia markers CA IX and GLUT I and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy chemotherapy [J].
De Schutter, H ;
Landuyt, W ;
Verbeken, E ;
Goethals, L ;
Hermans, R ;
Nuyts, S .
BMC CANCER, 2005, 5 (1)
[9]   Tumor-Associated Lymphocytes As an Independent Predictor of Response to Neoadjuvant Chemotherapy in Breast Cancer [J].
Denkert, Carsten ;
Loibl, Sibylle ;
Noske, Aurelia ;
Roller, Marc ;
Mueller, Berit Maria ;
Komor, Martina ;
Budczies, Jan ;
Darb-Esfahani, Silvia ;
Kronenwett, Ralf ;
Hanusch, Claus ;
von Toerne, Christian ;
Weichert, Wilko ;
Engels, Knut ;
Solbach, Christine ;
Schrader, Iris ;
Dietel, Manfred ;
von Minckwitz, Gunter .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (01) :105-113
[10]   Estimates of cancer incidence and mortality in Europe in 2008 [J].
Ferlay, J. ;
Parkin, D. M. ;
Steliarova-Foucher, E. .
EUROPEAN JOURNAL OF CANCER, 2010, 46 (04) :765-781