title: Integration of epidemiology, immunobiology, and translational research for brain tumors.
abstract: We recently identified a pivotal role for the host type I interferon (IFN) pathway in immunosurveillance against de novo mouse glioma development, especially through the regulation of immature myeloid cells (IMCs) in the glioma microenvironment. The present paper summarizes our published work in a number of areas. We have identified single-nucleotide polymorphisms (SNPs) in human IFN genes that dictate altered prognosis of patients with glioma. One of these SNPs (rs12553612) is located in the promoter of IFNA8 and influences its activity. Conversely, recent epidemiologic data show that chronic use of nonsteroidal anti-inflammatory drugs lowers the risk of glioma. We translated these findings back to our de novo glioma model and found that cyclooxygenase-2 inhibition enhances antiglioma immunosurveillance by reducing glioma-associated IMCs. Taken together, these findings suggest that alterations in myeloid cell function condition the brain for glioma development. Finally, in preliminary work, we have begun applying novel immunotherapeutic approaches to patients with low-grade glioma with the aim of preventing malignant transformation. Future research will hopefully better integrate epidemiological, immunobiological, and translational techniques to develop novel, preventive approaches for malignant gliomas.
authors: University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA. okadah@upmc.edu
authors: Hideho
authors: H
authors: Okada
authors: Michael E
authors: ME
authors: Scheurer
authors: Saumendra N
authors: SN
authors: Sarkar
authors: Melissa L
authors: ML
authors: Bondy
mesh_terms: D000486:Allergy and Immunology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001932:Brain Neoplasms / Q000453:epidemiology* / Q000276:immunology / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D005910:Glioma / Q000453:epidemiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007249:Inflammation; D007370:Interferon Type I / Q000276:immunology*; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D057170:Translational Research, Biomedical
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007370:Interferon Type I; D051546:Cyclooxygenase 2
references: Neuro Oncol. 2011 Feb;13(2):242-50
references: 21149253
references: J Clin Oncol. 2002 Apr 15;20(8):2076-84
references: 11956268
references: Cancer Res. 2011 Apr 1;71(7):2664-74
references: 21324923
references: Clin Cancer Res. 1999 May;5(5):985-90
references: 10353730
references: J Natl Cancer Inst. 2007 Oct 17;99(20):1544-50
references: 17925535
references: Cancer Gene Ther. 2003 Jul;10(7):549-58
references: 12833135
references: Lancet Oncol. 2005 Apr;6(4):240-4
references: 15811619
references: Circulation. 2008 Apr 22;117(16):2104-13
references: 18378608
references: Clin Cancer Res. 2008 Oct 15;14(20):6640-6
references: 18927306
references: Cancer Res. 2007 May 1;67(9):4507-13
references: 17483367
references: Cancer Res. 2009 Jan 15;69(2):431-9
references: 19147555
references: Ann Oncol. 2008 Sep;19 Suppl 7:vii217-22
references: 18790954
references: J Transl Med. 2007 Feb 12;5:10
references: 17295916
references: Brain Tumor Pathol. 2004;21(3):113-6
references: 15696971
references: J Neurooncol. 2005 May;72(3):231-8
references: 15937645
references: Mol Cancer Res. 2005 Oct;3(10):541-51
references: 16254188
references: Int J Cancer. 2011 Nov 1;129(9):2290-6
references: 21190193
references: Lancet. 2005 Sep 17-23;366(9490):985-90
references: 16168780
references: J Neurosurg. 2008 Nov;109(5):835-41
references: 18976072
references: Cancer Res. 2006 Apr 15;66(8):4531-41
references: 16618782
references: Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1229-35
references: 17548690
references: Immunol Rev. 2008 Apr;222:180-91
references: 18364002
references: Neoplasia. 2005 Aug;7(8):717-22
references: 16207473
references: Curr Neurol Neurosci Rep. 2004 May;4(3):211-7
references: 15102347
references: J Clin Oncol. 2002 May 1;20(9):2267-76
references: 11980997
references: Cancer Res. 2006 Jun 1;66(11):5883-91
references: 16740728
references: Cancer Res. 2006 Apr 15;66(8):4478-87
references: 16618775
references: Cancer Epidemiol Biomarkers Prev. 2008 May;17(5):1277-81
references: 18483351
references: Cancer Immunol Immunother. 2010 Sep;59(9):1401-9
references: 20549206
references: Am J Epidemiol. 2004 Jun 15;159(12):1131-9
references: 15191930
references: Clin Cancer Res. 2008 Apr 1;14(7):2088-94
references: 18381949
references: Cancer Immunol Immunother. 2008 Dec;57(12):1827-35
references: 18438666
references: Int J Cancer. 2002 May 10;99(2):252-9
references: 11979441
references: Clin Cancer Res. 2007 Jan 15;13(2 Pt 2):721s-726s
references: 17255300
references: Cancer Res. 2005 Jul 15;65(14):6459-65
references: 16024651
references: Cancer Res. 2001 Feb 1;61(3):869-72
references: 11221872
references: Cancer Epidemiol Biomarkers Prev. 2007 Nov;16(11):2448-54
references: 18006935
references: Cancer. 2005 Jan 15;103(2):329-38
references: 15558802
references: Mol Med. 2000 May;6(5):440-9
references: 10952023
references: Gene Ther. 2004 Nov;11(21):1551-8
references: 15343358
references: Nat Clin Pract Neurol. 2006 Sep;2(9):494-503; quiz 1 p following 516
references: 16932614
references: Am J Ther. 2004 Mar-Apr;11(2):141-3
references: 14999366
references: Nat Med. 2012 Jan 26;18(4):624-9
references: 22281806
references: J Clin Oncol. 2011 Jan 20;29(3):330-6
references: 21149657
references: J Neurosurg. 2011 Nov;115(5):948-65
references: 22043865
references: Int J Cancer. 2002 Apr 1;98(4):609-15
references: 11920623
references: Neurol Clin. 2007 Nov;25(4):867-90, vii
references: 17964019
references: J Immunol. 2005 Aug 15;175(4):2730-40
references: 16081851
references: Carcinogenesis. 2007 Dec;28(12):2543-7
references: 17916900
references: Leuk Lymphoma. 2009 Feb;50(2):260-9
references: 19197722
references: Int J Radiat Oncol Biol Phys. 2002 Feb 1;52(2):316-24
references: 11872276
references: Int J Cancer. 2006 Nov 1;119(9):2165-72
references: 16823851
references: Carcinogenesis. 2010 Oct;31(10):1770-7
references: 20668009
references: Int J Radiat Oncol Biol Phys. 1996 Oct 1;36(3):549-56
references: 8948338
references: Oncology. 2007;73(1-2):21-5
references: 18332649
references: N Engl J Med. 2009 Feb 19;360(8):765-73
references: 19228619
references: Oncoimmunology. 2012 Jul 1;1(4):487-492
references: 22754767
references: Neuro Oncol. 2010 Apr;12(4):320-7
references: 20308310
references: Clin Cancer Res. 2002 Sep;8(9):2851-5
references: 12231526
references: Neuro Oncol. 2010 May;12(5):444-52
references: 20406895
references: Clin Cancer Res. 2010 Jul 1;16(13):3409-19
references: 20472682