Display options
Cite
Layer JP, Kronmüller MT, Quast T, et al. Amplification of N-Myc is associated with a T-cell-poor microenvironment in metastatic neuroblastoma restraining interferon pathway activity and chemokine expression. Oncoimmunology. 2017;6(6):e1320626doi: 10.1080/2162402X.2017.1320626.
Layer, J. P., Kronmüller, M. T., Quast, T., van den Boorn-Konijnenberg, D., Effern, M., Hinze, D., Althoff, K., Schramm, A., Westermann, F., Peifer, M., Hartmann, G., Tüting, T., Kolanus, W., Fischer, M., Schulte, J., & Hölzel, M. (2017). Amplification of N-Myc is associated with a T-cell-poor microenvironment in metastatic neuroblastoma restraining interferon pathway activity and chemokine expression. Oncoimmunology, 6(6), e1320626. https://doi.org/10.1080/2162402X.2017.1320626
Layer, Julian P, et al. "Amplification of N-Myc is associated with a T-cell-poor microenvironment in metastatic neuroblastoma restraining interferon pathway activity and chemokine expression." Oncoimmunology vol. 6,6 (2017): e1320626. doi: https://doi.org/10.1080/2162402X.2017.1320626
Layer JP, Kronmüller MT, Quast T, van den Boorn-Konijnenberg D, Effern M, Hinze D, Althoff K, Schramm A, Westermann F, Peifer M, Hartmann G, Tüting T, Kolanus W, Fischer M, Schulte J, Hölzel M. Amplification of N-Myc is associated with a T-cell-poor microenvironment in metastatic neuroblastoma restraining interferon pathway activity and chemokine expression. Oncoimmunology. 2017 Apr 28;6(6):e1320626. doi: 10.1080/2162402X.2017.1320626. eCollection 2017. PMID: 28680756; PMCID: PMC5486176.
Copy Download .nbib Format: NLM
Share it on

Oncoimmunology. 2017 Apr 28;6(6):e1320626. doi: 10.1080/2162402X.2017.1320626. eCollection 2017.

Amplification of N-Myc is associated with a T-cell-poor microenvironment in metastatic neuroblastoma restraining interferon pathway activity and chemokine expression.

Oncoimmunology

Julian P Layer, Marie T Kronmüller, Thomas Quast, Debby van den Boorn-Konijnenberg, Maike Effern, Daniel Hinze, Kristina Althoff, Alexander Schramm, Frank Westermann, Martin Peifer, Gunther Hartmann, Thomas Tüting, Waldemar Kolanus, Matthias Fischer, Johannes Schulte, Michael Hölzel

Affiliations

  1. Unit for RNA Biology, Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.
  2. Division of Molecular Immunology and Cell Biology, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
  3. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunology, The University of Melbourne, Melbourne, Victoria, Australia.
  4. Pediatric Oncology and Hematology, University Children's Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  5. Molecular Oncology, Internal Medicine/Cancer Research Unit, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  6. Neuroblastoma Genomics B087, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  7. Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, Cologne, Germany.
  8. Center for Molecular Medicine Cologne, Medical Faculty, University of Cologne, Cologne, Germany.
  9. Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.
  10. Laboratory of Experimental Dermatology, Department of Dermatology, University of Magdeburg, Magdeburg, Germany.
  11. Laboratory of Experimental Dermatology, Department of Dermatology, University of Bonn, Bonn, Germany.
  12. Department of Experimental Pediatric Hematology and Oncology, University of Cologne, Cologne, Germany.
  13. Max Planck Institute for Metabolism Research, Cologne, Germany.
  14. Department of Pediatric Hematology, Oncology and SCT, Charité - University Hospital Berlin, Campus Virchow-Klinikum, Berlin, Germany.

PMID: 28680756 PMCID: PMC5486176 DOI: 10.1080/2162402X.2017.1320626

Abstract

Immune checkpoint inhibitors have significantly improved the treatment of several cancers. T-cell infiltration and the number of neoantigens caused by tumor-specific mutations are correlated to favorable responses in cancers with a high mutation load. Accordingly, checkpoint immunotherapy is thought to be less effective in tumors with low mutation frequencies such as neuroblastoma, a neuroendocrine tumor of early childhood with poor outcome of the high-risk disease group. However, spontaneous regressions and paraneoplastic syndromes seen in neuroblastoma patients suggest substantial immunogenicity. Using an integrative transcriptomic approach, we investigated the molecular characteristics of T-cell infiltration in primary neuroblastomas as an indicator of pre-existing immune responses and potential responsiveness to checkpoint inhibition. Here, we report that a T-cell-poor microenvironment in primary metastatic neuroblastomas is associated with genomic amplification of the

Keywords: Chemokine; Cxcl10; N-Myc; STING; immunotherapy; infiltration; interferoninfiltration; neuroblastoma

References

  1. N Engl J Med. 2015 Oct 22;373(17):1627-39 - PubMed
  2. Cancer Discov. 2014 Jun;4(6):674-87 - PubMed
  3. Nat Med. 2015 Aug;21(8):938-45 - PubMed
  4. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50 - PubMed
  5. J Natl Cancer Inst. 1995 Oct 4;87(19):1470-6 - PubMed
  6. Med Pediatr Oncol. 2001 Jun;36(6):612-22 - PubMed
  7. Nucleic Acids Res. 2013 May 1;41(10):e108 - PubMed
  8. Cancer Res. 2016 Jan 15;76(2):251-63 - PubMed
  9. Oncogene. 2005 Jul 7;24(29):4634-44 - PubMed
  10. Semin Oncol. 2015 Aug;42(4):663-71 - PubMed
  11. Nature. 2014 Nov 27;515(7528):568-71 - PubMed
  12. Int J Cancer. 2007 Apr 1;120(7):1387-95 - PubMed
  13. Science. 2015 Apr 3;348(6230):124-8 - PubMed
  14. Cell Syst. 2015 Dec 23;1(6):417-425 - PubMed
  15. Am J Clin Pathol. 2005 Jul;124(1):37-48 - PubMed
  16. Sci Transl Med. 2015 Apr 15;7(283):283ra52 - PubMed
  17. Genome Biol. 2014 Feb 03;15(2):R29 - PubMed
  18. Med Pediatr Oncol. 2001 Jun;36(6):623-9 - PubMed
  19. EMBO J. 2013 May 15;32(10):1440-50 - PubMed
  20. Cell. 2013 Aug 15;154(4):748-62 - PubMed
  21. Cancer Res. 2016 Jan 15;76(2):275-82 - PubMed
  22. Genome Biol. 2015 Jun 25;16:133 - PubMed
  23. Nature. 2015 Oct 29;526(7575):700-4 - PubMed
  24. N Engl J Med. 2015 Nov 5;373(19):1803-13 - PubMed
  25. Nature. 2013 Jul 11;499(7457):214-8 - PubMed
  26. Oncogene. 2015 Jun;34(26):3357-68 - PubMed
  27. EMBO J. 1988 Apr;7(4):1023-9 - PubMed
  28. Curr Top Dev Biol. 2011;94:77-127 - PubMed
  29. N Engl J Med. 2016 Jul 21;375(3):296-7 - PubMed
  30. J Pediatr Hematol Oncol. 2000 Jul-Aug;22(4):315-20 - PubMed
  31. Nature. 2015 Nov 12;527(7577):249-53 - PubMed
  32. N Engl J Med. 2015 Jan 22;372(4):320-30 - PubMed
  33. Nat Genet. 2013 Mar;45(3):279-84 - PubMed
  34. Nat Rev Immunol. 2016 Sep;16(9):566-80 - PubMed
  35. Curr Opin Immunol. 2016 Aug;41:98-103 - PubMed
  36. Cell. 1986 Dec 5;47(5):667-74 - PubMed
  37. Nat Commun. 2015 Nov 04;6:8755 - PubMed
  38. Nature. 2011 Nov 09;479(7374):547-51 - PubMed
  39. J Clin Invest. 2007 Sep;117(9):2702-12 - PubMed
  40. Nature. 2007 Feb 8;445(7128):656-60 - PubMed
  41. J Clin Oncol. 2008 Mar 20;26(9):1504-10 - PubMed
  42. Cancer Res. 2009 Apr 1;69(7):3077-85 - PubMed
  43. Drugs. 2016 Jun;76(9):925-45 - PubMed
  44. Oncoimmunology. 2015 Jan 7;3(12):e954868 - PubMed
  45. Immunity. 2013 Oct 17;39(4):782-95 - PubMed
  46. Oncoimmunology. 2015 Apr 2;4(9):e1019981 - PubMed
  47. J Exp Med. 2004 May 3;199(9):1213-21 - PubMed
  48. EMBO J. 1997 Jun 2;16(11):2985-95 - PubMed
  49. Immunity. 2014 Nov 20;41(5):830-42 - PubMed
  50. Science. 2015 Oct 9;350(6257):207-11 - PubMed
  51. Nature. 2014 Nov 27;515(7528):577-81 - PubMed
  52. Nat Rev Clin Oncol. 2014 Dec;11(12):704-13 - PubMed
  53. N Engl J Med. 2015 May 21;372(21):2018-28 - PubMed
  54. Cell Rep. 2015 May 19;11(7):1018-30 - PubMed
  55. Nat Rev Cancer. 2013 Jun;13(6):397-411 - PubMed
  56. Cancer Immunol Res. 2016 Dec;4(12 ):1061-1071 - PubMed
  57. Cell. 2016 Mar 24;165(1):35-44 - PubMed
  58. Sci Transl Med. 2012 Mar 28;4(127):127ra37 - PubMed
  59. Trends Immunol. 2015 Apr;36(4):265-76 - PubMed
  60. N Engl J Med. 2014 Dec 4;371(23 ):2189-99 - PubMed
  61. J Immunother Cancer. 2015 Dec 15;3:42 - PubMed
  62. Cell. 2016 Dec 1;167(6):1540-1554.e12 - PubMed
  63. Nat Methods. 2015 May;12(5):453-7 - PubMed
  64. Genes Dev. 2002 Oct 15;16(20):2699-712 - PubMed

Publication Types