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Favorable prognostic influence of T-box transcription factor Eomesodermin in metastatic renal cell cancer patients

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Abstract

T-box transcription factors, T-box expressed in T cells (T-bet) encoded by Tbx21 and Eomesodermin (Eomes), drive the differentiation of effector/memory T cell lineages and NK cells. The aim of the study was to determine the prognostic influence of the expression of these transcription factors in peripheral blood (pB) in a cohort of 41 metastatic (m) RCC patients before receiving sorafenib treatment and to analyze their association with the immunophenotype in pB. In contrast to Tbx21, in the multivariate analysis including clinical features, Eomes mRNA expression was identified as an independent good prognostic factor for progression-free survival (PFS, p = 0.042) and overall survival (OS, p = 0.001) in addition to a favorable ECOG performance status (p = 0.01 and p = 0.008, respectively). Eomes expression correlated positively not only with expression of Tbx21 and TGFβ1 mRNA, but also with mRNA expression of the activation marker ICOS, and with in vivo activated HLA-DR+ T cells. Eomes expression was negatively associated with TNFα-producing T cells. On protein level, Eomes was mainly expressed by CD56+CD3− NK cells in pB. In conclusion, we identified a higher Eomes mRNA expression as an independent good prognostic factor for OS and PFS in mRCC patients treated with sorafenib.

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Abbreviations

AP:

Alkaline phosphatase

Ca:

Corrected serum calcium concentrations

CAF:

Cytokine and angiogenic factor

CCR:

C–C chemokine receptor

CD:

Cluster of differentiation

CT:

X-ray computed tomography

CTL:

Cytotoxic T cells

ECOG:

Eastern Cooperative Oncology Group

Eomes:

Eomesodermin

Hb:

Hemoglobin

HLA-DR:

Human leukocyte antigen class II

HMBS:

Hydroxymethylbilane synthase

ICOS:

Inducible T cell co-stimulator

IFN:

Interferon

IL:

Interleukin

mAb:

Monoclonal antibody

MDSC:

Myeloid-derived suppressor cells

MFI:

Mean fluorescence intensity

mRCC:

Metastatic renal cell cancer

MRI:

Magnetic resonance imaging

mRNA:

Messenger ribonucleic acid

MSKCC:

Memorial Sloan-Kettering Cancer Center score

mTOR:

Mechanistic target of rapamycin, previously known as mammalian target of rapamycin

NK cells:

Natural killer cells

NKT cells:

Natural killer T cells

OS:

Overall survival

pB:

Peripheral blood

PBGD:

Porphobilinogen deaminase

PBMCs:

Peripheral blood mononuclear cells

PFS:

Progression-free survival

PMA:

Phorbol 12-myristate 13-acetate

RECIST:

Response Evaluation Criteria in Solid Tumors

RT-PCR:

Reverse transcriptase polymerase chain reaction

T-bet:

T-box expressed in T cells

TCM :

Central memory T cells

TE :

Effector T cells

TEM :

Effector memory T cells

TGF:

Transforming growth factor

Th1:

Type 1 T helper cells

TKI:

Tyrosine kinase inhibitor

TNF:

Tumor necrosis factor

Treg:

Regulatory T cells

VEGF:

Vascular endothelial growth factor

References

  1. Busse A, Keilholz U (2010) Immune self-tuning in renal cell carcinoma. Eur Oncol 6(1):70–75

    Google Scholar 

  2. Knox JJ, Cosma GL, Betts MR, McLane LM (2014) Characterization of T-bet and eomes in peripheral human immune cells. Front Immunol 5:217. doi:10.3389/fimmu.2014.00217

    Article  PubMed Central  PubMed  Google Scholar 

  3. Intlekofer AM, Takemoto N, Wherry EJ, Longworth SA, Northrup JT, Palanivel VR, Mullen AC, Gasink CR, Kaech SM, Miller JD, Gapin L, Ryan K, Russ AP, Lindsten T, Orange JS, Goldrath AW, Ahmed R, Reiner SL (2005) Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin. Nat Immunol 6(12):1236–1244. doi:10.1038/ni1268

    Article  CAS  PubMed  Google Scholar 

  4. Rao RR, Li Q, Odunsi K, Shrikant PA (2010) The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T-bet and Eomesodermin. Immunity 32(1):67–78. doi:10.1016/j.immuni.2009.10.010

    Article  PubMed  Google Scholar 

  5. Gordon SM, Chaix J, Rupp LJ, Wu J, Madera S, Sun JC, Lindsten T, Reiner SL (2012) The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation. Immunity 36(1):55–67. doi:10.1016/j.immuni.2011.11.016

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Townsend MJ, Weinmann AS, Matsuda JL, Salomon R, Farnham PJ, Biron CA, Gapin L, Glimcher LH (2004) T-bet regulates the terminal maturation and homeostasis of NK and Valpha14i NKT cells. Immunity 20(4):477–494

    Article  CAS  PubMed  Google Scholar 

  7. Beuselinck B, Vano YA, Oudard S, Wolter P, De Smet R, Depoorter L, Teghom C, Karadimou A, Zucman-Rossi J, Debruyne PR, Van Poppel H, Joniau S, Lerut E, Strijbos M, Dumez H, Paridaens R, Van Calster B, Schoffski P (2014) Prognostic impact of baseline serum C-reactive protein in patients with metastatic renal cell carcinoma (RCC) treated with sunitinib. BJU Int 114(1):81–89. doi:10.1111/bju.12494

    Article  CAS  PubMed  Google Scholar 

  8. Zhu Y, Ju S, Chen E, Dai S, Li C, Morel P, Liu L, Zhang X, Lu B (2010) T-bet and eomesodermin are required for T cell-mediated antitumor immune responses. J Immunol 185(6):3174–3183. doi:10.4049/jimmunol.1000749

    Article  CAS  PubMed  Google Scholar 

  9. Pearce EL, Mullen AC, Martins GA, Krawczyk CM, Hutchins AS, Zediak VP, Banica M, DiCioccio CB, Gross DA, Mao CA, Shen H, Cereb N, Yang SY, Lindsten T, Rossant J, Hunter CA, Reiner SL (2003) Control of effector CD8+ T cell function by the transcription factor Eomesodermin. Science 302(5647):1041–1043. doi:10.1126/science.1090148

    Article  CAS  PubMed  Google Scholar 

  10. Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, Eigl BJ, Ruether JD, Cheng T, North S, Venner P, Knox JJ, Chi KN, Kollmannsberger C, McDermott DF, Oh WK, Atkins MB, Bukowski RM, Rini BI, Choueiri TK (2009) Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 27(34):5794–5799. doi:10.1200/JCO.2008.21.4809

    Article  CAS  PubMed  Google Scholar 

  11. Yasuda Y, Saito K, Yuasa T, Kitsukawa S, Urakami S, Yamamoto S, Yonese J, Takahashi S, Fukui I (2013) Prognostic impact of pretreatment C-reactive protein for patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors. Int J Clin Oncol 18(5):884–889. doi:10.1007/s10147-012-0454-0

    Article  CAS  PubMed  Google Scholar 

  12. Polimeno M, Napolitano M, Costantini S, Portella L, Esposito A, Capone F, Guerriero E, Trotta A, Zanotta S, Pucci L, Longo N, Perdona S, Pignata S, Castello G, Scala S (2013) Regulatory T cells, interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), CXCL10, CXCL11, epidermal growth factor (EGF) and hepatocyte growth factor (HGF) as surrogate markers of host immunity in patients with renal cell carcinoma. BJU Int 112(5):686–696. doi:10.1111/bju.12068

    Article  CAS  PubMed  Google Scholar 

  13. Funakoshi T, Lee CH, Hsieh JJ (2014) A systematic review of predictive and prognostic biomarkers for VEGF-targeted therapy in renal cell carcinoma. Cancer Treat Rev 40(4):533–547. doi:10.1016/j.ctrv.2013.11.008

    Article  CAS  PubMed  Google Scholar 

  14. Tran HT, Liu Y, Zurita AJ, Lin Y, Baker-Neblett KL, Martin AM, Figlin RA, Hutson TE, Sternberg CN, Amado RG, Pandite LN, Heymach JV (2012) Prognostic or predictive plasma cytokines and angiogenic factors for patients treated with pazopanib for metastatic renal-cell cancer: a retrospective analysis of phase 2 and phase 3 trials. Lancet Oncol 13(8):827–837. doi:10.1016/S1470-2045(12)70241-3

    Article  CAS  PubMed  Google Scholar 

  15. Busse A, Asemissen A, Nonnenmacher A, Ochsenreither S, Fusi A, Braun F, Stather D, Schmittel A, Miller K, Thiel E, Keilholz U (2011) Systemic immune tuning in renal cell carcinoma: favorable prognostic impact of TGF-beta1 mRNA expression in peripheral blood mononuclear cells. J Immunother 34(1):113–119. doi:10.1097/CJI.0b013e3181fb6580

    Article  CAS  PubMed  Google Scholar 

  16. 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 (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313(5795):1960–1964. doi:10.1126/science.1129139

    Article  CAS  PubMed  Google Scholar 

  17. Pages F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D, Meatchi T, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Galon J (2005) Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 353(25):2654–2666. doi:10.1056/NEJMoa051424

    Article  CAS  PubMed  Google Scholar 

  18. Atreya I, Schimanski CC, Becker C, Wirtz S, Dornhoff H, Schnurer E, Berger MR, Galle PR, Herr W, Neurath MF (2007) The T-box transcription factor eomesodermin controls CD8 T cell activity and lymph node metastasis in human colorectal cancer. Gut 56(11):1572–1578. doi:10.1136/gut.2006.117812

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Chen LJ, Zheng X, Shen YP, Zhu YB, Li Q, Chen J, Xia R, Zhou SM, Wu CP, Zhang XG, Lu BF, Jiang JT (2013) Higher numbers of T-bet(+) intratumoral lymphoid cells correlate with better survival in gastric cancer. Cancer Immunol Immunother 62(3):553–561. doi:10.1007/s00262-012-1358-6

    Article  CAS  PubMed  Google Scholar 

  20. Therasse P (2002) Measuring the clinical response. What does it mean? Eur J Cancer 38(14):1817–1823

    Article  CAS  PubMed  Google Scholar 

  21. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5(6):649–655

    Article  CAS  PubMed  Google Scholar 

  22. Motzer RJ, Bacik J, Schwartz LH, Reuter V, Russo P, Marion S, Mazumdar M (2004) Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol 22(3):454–463

    Article  PubMed  Google Scholar 

  23. Busse A, Asemissen AM, Nonnenmacher A, Braun F, Ochsenreither S, Stather D, Fusi A, Schmittel A, Miller K, Thiel E, Keilholz U (2011) Immunomodulatory effects of sorafenib on peripheral immune effector cells in metastatic renal cell carcinoma. Eur J Cancer 47(5):690–696. doi:10.1016/j.ejca.2010.11.021

    Article  CAS  PubMed  Google Scholar 

  24. Roosen JU, Engel U, Jensen RH, Kvist E, Schou G (1994) Renal cell carcinoma: prognostic factors. Br J Urol 74(2):160–164

    Article  CAS  PubMed  Google Scholar 

  25. Finley DS, Pantuck AJ, Belldegrun AS (2011) Tumor biology and prognostic factors in renal cell carcinoma. Oncologist 16(Suppl 2):4–13. doi:10.1634/theoncologist.2011-S2-04

    Article  PubMed Central  PubMed  Google Scholar 

  26. Brannon AR, Haake SM, Hacker KE, Pruthi RS, Wallen EM, Nielsen ME, Rathmell WK (2012) Meta-analysis of clear cell renal cell carcinoma gene expression defines a variant subgroup and identifies gender influences on tumor biology. Eur Urol 61(2):258–268. doi:10.1016/j.eururo.2011.10.007

    Article  PubMed Central  PubMed  Google Scholar 

  27. Maroto P, Rini B (2014) Molecular biomarkers in advanced renal cell carcinoma. Clin Cancer Res 20(8):2060–2071. doi:10.1158/1078-0432.CCR-13-1351

    Article  CAS  PubMed  Google Scholar 

  28. Poli A, Michel T, Theresine M, Andres E, Hentges F, Zimmer J (2009) CD56bright natural killer (NK) cells: an important NK cell subset. Immunology 126(4):458–465. doi:10.1111/j.1365-2567.2008.03027.x

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Cheng M, Chen Y, Xiao W, Sun R, Tian Z (2013) NK cell-based immunotherapy for malignant diseases. Cell Mol Immunol 10(3):230–252. doi:10.1038/cmi.2013.10

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Schleypen JS, Baur N, Kammerer R, Nelson PJ, Rohrmann K, Grone EF, Hohenfellner M, Haferkamp A, Pohla H, Schendel DJ, Falk CS, Noessner E (2006) Cytotoxic markers and frequency predict functional capacity of natural killer cells infiltrating renal cell carcinoma. Clin Cancer Res 12(3 Pt 1):718–725. doi:10.1158/1078-0432.CCR-05-0857

    Article  CAS  PubMed  Google Scholar 

  31. Takai S, Schlom J, Tucker J, Tsang KY, Greiner JW (2013) Inhibition of TGF-beta1 signaling promotes central memory T cell differentiation. J Immunol 191(5):2299–2307. doi:10.4049/jimmunol.1300472

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Mantovani A, Garlanda C, Allavena P (2010) Molecular pathways and targets in cancer-related inflammation. Ann Med 42(3):161–170. doi:10.3109/07853890903405753

    Article  CAS  PubMed  Google Scholar 

  33. Tofukuji S, Kuwahara M, Suzuki J, Ohara O, Nakayama T, Yamashita M (2012) Identification of a new pathway for Th1 cell development induced by cooperative stimulation with IL-4 and TGF-beta. J Immunol 188(10):4846–4857. doi:10.4049/jimmunol.1103799

    Article  CAS  PubMed  Google Scholar 

  34. Lingnau K, Hoehn P, Kerdine S, Koelsch S, Neudoerfl C, Palm N, Ruede E, Schmitt E (1998) IL-4 in combination with TGF-beta favors an alternative pathway of Th1 development independent of IL-12. J Immunol 161(9):4709–4718

    CAS  PubMed  Google Scholar 

  35. Eshima K, Chiba S, Suzuki H, Kokubo K, Kobayashi H, Iizuka M, Iwabuchi K, Shinohara N (2012) Ectopic expression of a T-box transcription factor, eomesodermin, renders CD4(+) Th cells cytotoxic by activating both perforin- and FasL-pathways. Immunol Lett 144(1–2):7–15. doi:10.1016/j.imlet.2012.02.013

    Article  CAS  PubMed  Google Scholar 

  36. Hu Q, Gou Y, Sun C, Ding W, Xu K, Gu B, Xia G, Ding Q (2014) The prognostic value of C-reactive protein in renal cell carcinoma: a systematic review and meta-analysis. Urologic oncology 32(1):50e1–50e8. doi:10.1016/j.urolonc.2013.07.016

    Article  Google Scholar 

  37. Negrier S, Perol D, Menetrier-Caux C, Escudier B, Pallardy M, Ravaud A, Douillard JY, Chevreau C, Lasset C, Blay JY, Groupe Francais dI (2004) Interleukin-6, interleukin-10, and vascular endothelial growth factor in metastatic renal cell carcinoma: prognostic value of interleukin-6–from the Groupe Francais d’Immunotherapie. J Clin Oncol 22(12):2371–2378. doi:10.1200/JCO.2004.06.121

    Article  Google Scholar 

  38. Perez-Gracia JL, Prior C, Guillen-Grima F, Segura V, Gonzalez A, Panizo A, Melero I, Grande-Pulido E, Gurpide A, Gil-Bazo I, Calvo A (2009) Identification of TNF-alpha and MMP-9 as potential baseline predictive serum markers of sunitinib activity in patients with renal cell carcinoma using a human cytokine array. Br J Cancer 101(11):1876–1883. doi:10.1038/sj.bjc.6605409

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Vermaat JS, van der Tweel I, Mehra N, Sleijfer S, Haanen JB, Roodhart JM, Engwegen JY, Korse CM, Langenberg MH, Kruit W, Groenewegen G, Giles RH, Schellens JH, Beijnen JH, Voest EE (2010) Two-protein signature of novel serological markers apolipoprotein-A2 and serum amyloid alpha predicts prognosis in patients with metastatic renal cell cancer and improves the currently used prognostic survival models. Ann Oncol 21(7):1472–1481. doi:10.1093/annonc/mdp559

    Article  CAS  PubMed  Google Scholar 

  40. Sengupta S, Lohse CM, Cheville JC, Leibovich BC, Thompson RH, Webster WS, Frank I, Zincke H, Blute ML, Kwon ED (2006) The preoperative erythrocyte sedimentation rate is an independent prognostic factor in renal cell carcinoma. Cancer 106(2):304–312. doi:10.1002/cncr.21617

    Article  PubMed  Google Scholar 

  41. Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH (2000) A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100(6):655–669

    Article  CAS  PubMed  Google Scholar 

  42. Ylikoski E, Lund R, Kylaniemi M, Filen S, Kilpelainen M, Savolainen J, Lahesmaa R (2005) IL-12 up-regulates T-bet independently of IFN-gamma in human CD4+ T cells. Eur J Immunol 35(11):3297–3306. doi:10.1002/eji.200526101

    Article  CAS  PubMed  Google Scholar 

  43. Lin JT, Martin SL, Xia L, Gorham JD (2005) TGF-beta 1 uses distinct mechanisms to inhibit IFN-gamma expression in CD4+ T cells at priming and at recall: differential involvement of Stat4 and T-bet. J Immunol 174(10):5950–5958

    Article  CAS  PubMed  Google Scholar 

  44. Garcia-Roig M, Ortiz N, Lokeshwar V (2014) Molecular marker for predicting treatment response in advanced renal cell carcinoma: does the promise fulfill clinical need? Curr Urol Rep 15(1):375. doi:10.1007/s11934-013-0375-0

    Article  PubMed Central  PubMed  Google Scholar 

  45. Porta C, Paglino C, De Amici M, Quaglini S, Sacchi L, Imarisio I, Canipari C (2010) Predictive value of baseline serum vascular endothelial growth factor and neutrophil gelatinase-associated lipocalin in advanced kidney cancer patients receiving sunitinib. Kidney Int 77(9):809–815. doi:10.1038/ki.2009.552

    Article  CAS  PubMed  Google Scholar 

  46. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Staehler M, Negrier S, Chevreau C, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Anderson S, Hofilena G, Shan M, Pena C, Lathia C, Bukowski RM (2009) Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol 27(20):3312–3318

    Article  CAS  PubMed  Google Scholar 

  47. Harmon CS, DePrimo SE, Figlin RA, Hudes GR, Hutson TE, Michaelson MD, Negrier S, Kim ST, Huang X, Williams JA, Eisen T, Motzer RJ (2014) Circulating proteins as potential biomarkers of sunitinib and interferon-alpha efficacy in treatment-naive patients with metastatic renal cell carcinoma. Cancer Chemother Pharmacol 73(1):151–161. doi:10.1007/s00280-013-2333-4

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Pena C, Lathia C, Shan M, Escudier B, Bukowski RM (2010) Biomarkers predicting outcome in patients with advanced renal cell carcinoma: Results from sorafenib phase III Treatment Approaches in Renal Cancer Global Evaluation Trial. Clin Cancer Res 16(19):4853–4863. doi:10.1158/1078-0432.CCR-09-3343

    Article  CAS  PubMed  Google Scholar 

  49. Zurita AJ, Jonasch E, Wang X, Khajavi M, Yan S, Du DZ, Xu L, Herynk MH, McKee KS, Tran HT, Logothetis CJ, Tannir NM, Heymach JV (2012) A cytokine and angiogenic factor (CAF) analysis in plasma for selection of sorafenib therapy in patients with metastatic renal cell carcinoma. Ann Oncol 23(1):46–52. doi:10.1093/annonc/mdr047

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Hertoghs KM, Moerland PD, van Stijn A, Remmerswaal EB, Yong SL, van de Berg PJ, van Ham SM, Baas F, ten Berge IJ, van Lier RA (2010) Molecular profiling of cytomegalovirus-induced human CD8+ T cell differentiation. J Clin Investig 120(11):4077–4090. doi:10.1172/JCI42758

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank AnneMarie Asemissen for her support with collecting patient samples.

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Authors and Affiliations

  1. Department of Medicine III (Hematology, Oncology and Tumor Immunology), Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany

    Anastasia Dielmann, Anne Letsch, Anika Nonnenmacher, Ulrich Keilholz & Antonia Busse

  2. Department of Urology, Charité, Campus Benjamin Franklin, Berlin, Germany

    Kurt Miller

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  1. Anastasia Dielmann
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  2. Anne Letsch
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  3. Anika Nonnenmacher
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  4. Kurt Miller
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Correspondence to Antonia Busse.

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Dielmann, A., Letsch, A., Nonnenmacher, A. et al. Favorable prognostic influence of T-box transcription factor Eomesodermin in metastatic renal cell cancer patients. Cancer Immunol Immunother 65, 181–192 (2016). https://doi.org/10.1007/s00262-015-1786-1

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