title: The potential for genetically altered microglia to influence glioma treatment.
abstract: Diffuse and unstoppable infiltration of brain and spinal cord tissue by neoplastic glial cells is the single most important therapeutic problem posed by the common glioma group of tumors: astrocytoma, oligoastrocytoma, oligodendroglioma, their malignant variants and glioblastoma. These neoplasms account for more than two thirds of all malignant central nervous system tumors. However, most glioma research focuses on an examination of the tumor cells rather than on host-specific, tumor micro-environmental cells and factors. This can explain why existing diffuse glioma therapies fail and why these tumors have remained incurable. Thus, there is a great need for innovation. We describe a novel strategy for the development of a more effective treatment of diffuse glioma. Our approach centers on gaining control over the behavior of the microglia, the defense cells of the CNS, which are manipulated by malignant glioma and support its growth. Armoring microglia against the influences from glioma is one of our research goals. We further discuss how microglia precursors may be genetically enhanced to track down infiltrating glioma cells.
authors.affiliation: Brain and Mind Research Institute, The University of Sydney, Camperdown, NSW, Australia. manuel@graeber.net.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: R M D
authors.initials: RM
authors.lastname: Holsinger
authors.forename: C A
authors.initials: CA
authors.lastname: Kruse
authors.forename: A
authors.initials: A
authors.lastname: Flügel
authors.forename: M B
authors.initials: MB
authors.lastname: Graeber
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D053263:Gene Regulatory Networks / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods* / Q000639:trends; D005910:Glioma / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D017628:Microglia / Q000473:pathology / Q000502:physiology*; D016896:Treatment Outcome
references.citation: J Neuroimmunol. 1998 Jan;81(1-2):20-30
references.pmid: 9521602
references.citation: J Neurooncol. 1994;22(3):191-200
references.pmid: 7760095
references.citation: Nature. 2005 Jun 2;435(7042):646-51
references.pmid: 15806097
references.citation: J Immunol. 2006 Jan 1;176(1):491-5
references.pmid: 16365442
references.citation: Lymphokine Cytokine Res. 1993 Feb;12(1):25-32
references.pmid: 8457629
references.citation: J Biol Chem. 2000 Aug 25;275(34):26500-6
references.pmid: 10950967
references.citation: J Biol Chem. 2007 Apr 6;282(14):10172-9
references.pmid: 17287216
references.citation: J Immunol. 2006 Jun 15;176(12):7456-61
references.pmid: 16751391
references.citation: J Exp Med. 2005 Aug 15;202(4):551-60
references.pmid: 16087712
references.citation: Nat Immunol. 2007 Oct;8(10):1067-75
references.pmid: 17767160
references.citation: Cytokine. 2005 Feb 7;29(3):118-24
references.pmid: 15613279
references.citation: Am J Hum Genet. 2004 Mar;74(3):582-4; author reply 584-5
references.pmid: 14973784
references.citation: Am J Respir Cell Mol Biol. 2002 Nov;27(5):536-41
references.pmid: 12397012
references.citation: J Immunol. 2000 Jan 15;164(2):1086-95
references.pmid: 10623860
references.citation: Cell Signal. 2010 Oct;22(10):1485-94
references.pmid: 20570727
references.citation: Anal Biochem. 2008 May 15;376(2):206-12
references.pmid: 18328249
references.citation: Mod Pathol. 1996 Mar;9(3):316-9
references.pmid: 8685234
references.citation: J Biol Chem. 2005 Jul 1;280(26):24915-22
references.pmid: 15870068
references.citation: Biochim Biophys Acta. 2002 Nov 11;1592(3):237-50
references.pmid: 12421669
references.citation: J Immunol. 2005 Aug 15;175(4):2563-9
references.pmid: 16081830
references.citation: J Immunol. 1999 Feb 15;162(4):1999-2007
references.pmid: 9973471
references.citation: J Biol Chem. 1996 Oct 11;271(41):25555-61
references.pmid: 8810328
references.citation: Hum Mol Genet. 2000 Mar 1;9(4):549-59
references.pmid: 10699178
references.citation: J Biol Chem. 2002 Nov 8;277(45):43194-205
references.pmid: 12189139
references.citation: J Exp Med. 1998 Dec 21;188(12):2289-99
references.pmid: 9858515
references.citation: Eur Respir J. 2005 Nov;26(5):795-803
references.pmid: 16264039
references.citation: Cancer Biol Ther. 2012 Aug;13(10):836-9
references.pmid: 22785212
references.citation: J Biol Chem. 2004 Jun 11;279(24):25196-203
references.pmid: 15069079
references.citation: Infect Immun. 2002 Nov;70(11):6436-43
references.pmid: 12379724
references.citation: J Immunol. 2002 Feb 1;168(3):1139-45
references.pmid: 11801648
references.citation: Am J Respir Cell Mol Biol. 2008 Mar;38(3):310-7
references.pmid: 17901408
references.citation: Immunology. 2007 Apr;120(4):573-9
references.pmid: 17343616
references.citation: Immunology. 2006 Sep;119(1):54-62
references.pmid: 16764687
references.citation: Biochem Biophys Res Commun. 1993 Dec 30;197(3):1424-30
references.pmid: 8280160
references.citation: Clin Cancer Res. 2003 Dec 15;9(17):6381-8
references.pmid: 14695138
references.citation: J Immunol. 2007 Aug 15;179(4):2556-64
references.pmid: 17675518
references.citation: J Neurosci Res. 2001 Oct 1;66(1):74-82
references.pmid: 11599003
references.citation: Cell. 2011 Mar 4;144(5):646-74
references.pmid: 21376230
references.citation: J Immunol. 2005 Oct 15;175(8):5178-85
references.pmid: 16210622
references.citation: Am J Respir Crit Care Med. 2006 Jun 1;173(11):1216-21
references.pmid: 16528019
references.citation: Nature. 2012 Nov 1;491(7422):114-8
references.pmid: 23000899
references.citation: J Immunol. 2008 Mar 15;180(6):4191-9
references.pmid: 18322231
references.citation: Mol Cell Biol. 2002 Jan;22(1):117-26
references.pmid: 11739727
references.citation: J Exp Med. 2008 Oct 27;205(11):2595-608
references.pmid: 18852293
references.citation: Am J Respir Crit Care Med. 2003 Feb 1;167(3):319-32
references.pmid: 12554621
references.citation: Proteins. 2011 Jan;79(1):282-93
references.pmid: 21064130
references.citation: J Immunol. 2004 Apr 1;172(7):4545-55
references.pmid: 15034072
references.citation: Neurogenetics. 2004 Jun;5(2):95-108
references.pmid: 15042428
references.citation: J Leukoc Biol. 2007 Jan;81(1):336-43
references.pmid: 17041005
references.citation: J Biol Chem. 2003 Feb 7;278(6):3903-11
references.pmid: 12459556
references.citation: Int J Oncol. 2011 Jan;38(1):97-103
references.pmid: 21109930
references.citation: Cancer Res. 2005 Apr 1;65(7):2956-63
references.pmid: 15805299
references.citation: Science. 2009 Jul 24;325(5939):433
references.pmid: 19628861
references.citation: J Immunol. 1999 May 1;162(9):5224-9
references.pmid: 10227996
references.citation: J Immunol. 2005 Nov 1;175(9):6107-16
references.pmid: 16237107
references.citation: J Immunol. 2007 Jun 1;178(11):6886-93
references.pmid: 17513737
references.citation: Biotechnol Bioeng. 2010 May 1;106(1):97-105
references.pmid: 20047187
references.citation: Am J Respir Crit Care Med. 2002 Apr 15;165(8):1161-71
references.pmid: 11956062
references.citation: J Leukoc Biol. 2004 Nov;76(5):1019-27
references.pmid: 15316031
references.citation: J Immunol. 2001 Aug 1;167(3):1683-92
references.pmid: 11466392
references.citation: J Immunol. 2010 Jan 15;184(2):615-23
references.pmid: 20018622
references.citation: Am J Respir Cell Mol Biol. 2003 Jun;28(6):648-54
references.pmid: 12760962
references.citation: J Leukoc Biol. 2008 Sep;84(3):623-30
references.pmid: 18467655
references.citation: Cancer. 2004 Sep 1;101(5):1036-42
references.pmid: 15329913
references.citation: PLoS One. 2009;4(3):e4660
references.pmid: 19252738
references.citation: Clin Cancer Res. 2009 Aug 1;15(15):4925-34
references.pmid: 19638465
references.citation: Am J Hum Genet. 2002 Jan;70(1):230-6
references.pmid: 11709756
references.citation: J Immunol. 2006 Jan 15;176(2):819-26
references.pmid: 16393965
references.citation: J Biol Chem. 1997 Apr 4;272(14):9474-80
references.pmid: 9083087
references.citation: Cancer Res. 2003 Dec 1;63(23):8145-52
references.pmid: 14678968
references.citation: J Biol Chem. 2002 Nov 1;277(44):41906-15
references.pmid: 12194977
references.citation: Stem Cells Dev. 2009 Apr;18(3):511-9
references.pmid: 18624673
references.citation: Nat Rev Cancer. 2008 May;8(5):377-86
references.pmid: 18385683
references.citation: J Biol Chem. 1997 Feb 28;272(9):5487-94
references.pmid: 9038152
references.citation: J Immunol. 1999 Jul 1;163(1):337-42
references.pmid: 10384133
references.citation: J Biol Chem. 1999 Jul 23;274(30):20818-25
references.pmid: 10409622
references.citation: Clin Exp Immunol. 2005 Sep;141(3):459-66
references.pmid: 16045735
references.citation: BMC Biol. 2006 Apr 26;4:13
references.pmid: 16640778
references.citation: J Immunol. 2003 Aug 15;171(4):1891-900
references.pmid: 12902491
references.citation: Nucleic Acids Res. 2003 Jan 15;31(2):532-50
references.pmid: 12527760
references.citation: J Am Soc Nephrol. 2006 Oct;17(10):2844-53
references.pmid: 16914538
references.citation: J Immunol. 2007 Jan 1;178(1):219-27
references.pmid: 17182558
references.citation: J Immunol. 2009 Jul 1;183(1):155-63
references.pmid: 19535633
references.citation: BMC Blood Disord. 2012 May 14;12:5
references.pmid: 22583379
references.citation: Infect Immun. 2002 Mar;70(3):1627-30
references.pmid: 11854255
references.citation: Glia. 2011 Mar;59(3):472-85
references.pmid: 21264953
references.citation: J Biol Chem. 1995 Apr 14;270(15):8797-804
references.pmid: 7721786
references.citation: Cell Res. 2000 Dec;10(4):245-66
references.pmid: 11191348
references.citation: Am J Respir Cell Mol Biol. 1998 May;18(5):620-30
references.pmid: 9569232
references.citation: Mucosal Immunol. 2010 May;3(3):291-300
references.pmid: 20404812
references.citation: J Biol Chem. 2009 Feb 27;284(9):5763-73
references.pmid: 19109256
references.citation: J Clin Invest. 2003 Feb;111(3):291-7
references.pmid: 12569150
references.citation: Science. 2010 Nov 5;330(6005):783-8
references.pmid: 21051630
references.citation: J Immunol. 2005 Apr 15;174(8):4630-8
references.pmid: 15814686
references.citation: J Immunol. 2008 Apr 1;180(7):4371-81
references.pmid: 18354157
references.citation: J Immunol. 2010 Feb 15;184(4):1663-74
references.pmid: 20130218
references.citation: Semin Cancer Biol. 2008 Oct;18(5):349-55
references.pmid: 18467122
references.citation: Immunol Cell Biol. 2001 Aug;79(4):332-9
references.pmid: 11488979
references.citation: J Neuroimmunol. 2007 Feb;183(1-2):1-6
references.pmid: 17188367
references.citation: J Exp Med. 2009 Sep 28;206(10):2191-204
references.pmid: 19770271
references.citation: Cytokine. 1993 Jan;5(1):38-46
references.pmid: 8097934
references.citation: J Exp Med. 2009 Apr 13;206(4):877-92
references.pmid: 19349465
references.citation: J Clin Invest. 2002 May;109(10):1279-83
references.pmid: 12021241
references.citation: J Immunol. 2000 Nov 15;165(10):5573-9
references.pmid: 11067912
references.citation: Nat Biotechnol. 2011 Jan;29(1):64-7
references.pmid: 21151125
references.citation: J Immunol. 2002 Oct 1;169(7):3574-80
references.pmid: 12244147
references.citation: Am J Respir Crit Care Med. 2004 Mar 1;169(5):596-603
references.pmid: 14670803
references.citation: Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1156-60
references.pmid: 8577732
references.citation: Cancer Res. 2011 Feb 1;71(3):693-704
references.pmid: 21127196
references.citation: Am J Respir Cell Mol Biol. 2006 Feb;34(2):213-8
references.pmid: 16210693
references.citation: Clin Exp Allergy. 2000 Mar;30(3):348-55
references.pmid: 10691892
references.citation: Respir Res. 2005 Apr 13;6:34
references.pmid: 15829015
references.citation: Int Immunopharmacol. 2009 Feb;9(2):201-6
references.pmid: 19041426
references.citation: J Biol Chem. 1995 May 19;270(20):12286-96
references.pmid: 7744881
references.citation: J Pharmacol Exp Ther. 2008 Jun;325(3):882-92
references.pmid: 18337474
references.citation: J Biol Chem. 1995 Jan 13;270(2):966-70
references.pmid: 7822337
references.citation: Curr Opin HIV AIDS. 2011 Jan;6(1):74-9
references.pmid: 21242897
references.citation: J Immunol. 1998 Jan 1;160(1):60-8
references.pmid: 9551956
references.citation: J Immunol. 2010 Nov 1;185(9):5539-48
references.pmid: 20889544
references.citation: Immunol Rev. 2000 Aug;176:116-33
references.pmid: 11043772
references.citation: J Biol Chem. 2000 May 12;275(19):14375-80
references.pmid: 10799519
references.citation: Clin Cancer Res. 2010 Jan 15;16(2):577-86
references.pmid: 20068108
references.citation: Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10564-9
references.pmid: 9724743
references.citation: Arch Otolaryngol Head Neck Surg. 2008 Jun;134(6):630-5
references.pmid: 18559731
references.citation: J Immunol. 2009 Feb 1;182(3):1429-38
references.pmid: 19155490
references.citation: Am J Respir Cell Mol Biol. 2002 Nov;27(5):593-602
references.pmid: 12397019
references.citation: J Biol Chem. 1995 Feb 24;270(8):3512-7
references.pmid: 7876085
references.citation: Immunology. 2007 Nov;122(3):306-15
references.pmid: 17511808
references.citation: J Immunol. 2001 Aug 15;167(4):1962-9
references.pmid: 11489976
references.citation: Immunology. 2009 Jun;127(2):256-66
references.pmid: 19175798
references.citation: J Proteome Res. 2009 Jun;8(6):2873-81
references.pmid: 19351187
references.citation: Am J Respir Cell Mol Biol. 2001 Oct;25(4):522-30
references.pmid: 11694459
references.citation: Genes Dev. 2010 Mar 1;24(5):491-501
references.pmid: 20194441
references.citation: Science. 1991 May 10;252(5007):809-17
references.pmid: 2028256
references.citation: J Immunol. 2002 Jan 15;168(2):597-603
references.pmid: 11777951
references.citation: J Biol Chem. 1997 Mar 21;272(12):7927-31
references.pmid: 9065461
references.citation: Clin Exp Allergy. 2004 Aug;34(8):1202-8
references.pmid: 15298559
references.citation: J Infect Dis. 2007 Jan 1;195(1):21-9
references.pmid: 17152005
references.citation: J Immunol. 2003 May 15;170(10):5143-51
references.pmid: 12734361
references.citation: J Clin Invest. 2008 Nov;118(11):3546-56
references.pmid: 18982161
references.citation: J Immunol. 2007 Oct 15;179(8):5367-77
references.pmid: 17911623
references.citation: Cytokine. 1998 Oct;10(10):803-13
references.pmid: 9811535
references.citation: Glia. 1999 Mar;26(1):12-21
references.pmid: 10088668
references.citation: Arthritis Res Ther. 2006;8(2):205
references.pmid: 16542479
references.citation: J Clin Invest. 1996 Aug 1;98(3):604-9
references.pmid: 8698849
references.citation: PLoS One. 2010 Oct 01;5(10):
references.pmid: 20957211
references.citation: J Immunol. 2003 Jul 15;171(2):948-54
references.pmid: 12847266
references.citation: J Biol Chem. 1995 Jun 9;270(23):13869-78
references.pmid: 7775445
references.citation: Ann Biomed Eng. 2012 Feb;40(2):507-15
references.pmid: 21979168
references.citation: J Immunol. 2001 Dec 1;167(11):6382-7
references.pmid: 11714803
references.citation: Int Immunol. 2007 Feb;19(2):175-83
references.pmid: 17189592
references.citation: Blood. 2008 Sep 1;112(5):1784-93
references.pmid: 18579794
references.citation: EMBO J. 1985 Jun;4(6):1609-14
references.pmid: 4040853
references.citation: Clin Infect Dis. 2003 Oct 1;37 Suppl 3:S225-64
references.pmid: 12975753
references.citation: J Immunol. 2010 Apr 1;184(7):3955-63
references.pmid: 20181883
references.citation: Cell Immunol. 2004 May;229(1):41-51
references.pmid: 15331327
references.citation: Nature. 2012 Mar 18;484(7392):105-9
references.pmid: 22425995
references.citation: J Immunol. 2000 Sep 1;165(5):2818-23
references.pmid: 10946314
references.citation: Am J Respir Cell Mol Biol. 2004 Sep;31(3):257-65
references.pmid: 15087305
references.citation: Neurosci Bull. 2007 Nov;23(6):363-9
references.pmid: 18064067
references.citation: J Biol Chem. 1997 Sep 5;272(36):22940-7
references.pmid: 9278458
references.citation: Cell. 2010 May 28;141(5):775-85
references.pmid: 20510925
references.citation: J Immunol. 2001 Feb 1;166(3):1675-83
references.pmid: 11160210
references.citation: Nat Med. 2001 Dec;7(12):1356-61
references.pmid: 11726978
references.citation: J Immunol. 2001 Feb 15;166(4):2218-27
references.pmid: 11160275
references.citation: Biomaterials. 2012 Jun;33(16):4195-203
references.pmid: 22398206
references.citation: Am J Respir Crit Care Med. 2005 Sep 15;172(6):671-8
references.pmid: 15961692
references.citation: J Immunol. 2002 Nov 15;169(10):5796-804
references.pmid: 12421960
references.citation: Cancer Res. 2008 Jun 15;68(12):4614-22
references.pmid: 18559506
references.citation: J Immunol. 2009 Dec 15;183(12):7870-6
references.pmid: 20007572
references.citation: Mol Cancer Ther. 2003 Aug;2(8):783-7
references.pmid: 12939468
references.citation: Am J Respir Cell Mol Biol. 2004 Oct;31(4):456-62
references.pmid: 15231490
references.citation: J Leukoc Biol. 2009 May;85(5):844-54
references.pmid: 19179453
references.citation: Folia Psychiatr Neurol Jpn. 1954 Sep;8(2):99-126
references.pmid: 13232026
references.citation: J Clin Invest. 2006 Oct;116(10):2777-90
references.pmid: 17016559
references.citation: Am J Respir Cell Mol Biol. 2004 Nov;31(5):573-82
references.pmid: 15297269
references.citation: Infect Immun. 1999 Jul;67(7):3329-33
references.pmid: 10377109
references.citation: Hum Gene Ther. 2010 Jun;21(6):683-94
references.pmid: 20113165
references.citation: J Immunol. 1999 Sep 1;163(5):2432-42
references.pmid: 10452978
references.citation: J Immunol. 1996 May 1;156(9):3327-33
references.pmid: 8617957
references.citation: J Biol Chem. 2002 Nov 29;277(48):46073-8
references.pmid: 12354755
references.citation: J Immunol. 2004 Jan 15;172(2):1092-8
references.pmid: 14707083
references.citation: J Biol Chem. 1995 Sep 8;270(36):21326-30
references.pmid: 7673169
references.citation: Int Immunol. 2006 Sep;18(9):1397-404
references.pmid: 16914507
references.citation: Respir Res. 2008 Jan 15;9:4
references.pmid: 18197984
references.citation: J Cereb Blood Flow Metab. 2010 Jan;30(1):140-9
references.pmid: 19773802
references.citation: J Immunol. 1998 May 1;160(9):4622-7
references.pmid: 9574570
references.citation: Protein Expr Purif. 2008 Jul;60(1):25-30
references.pmid: 18467124
references.citation: Nature. 1986 Dec 18-31;324(6098):698-9
references.pmid: 3796733
references.citation: Immunology. 2000 Feb;99(2):272-8
references.pmid: 10692047
references.citation: J Immunol. 2006 Jan 15;176(2):1115-21
references.pmid: 16394000
references.citation: J Biol Chem. 2006 Feb 3;281(5):2414-29
references.pmid: 16251181
references.citation: Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):15018-23
references.pmid: 22923692
references.citation: J Immunol. 1998 Aug 15;161(4):1637-44
references.pmid: 9712025
references.citation: Neurogenetics. 2008 Feb;9(1):1-13
references.pmid: 18196299
references.citation: Biochem J. 1996 Nov 1;319 ( Pt 3):865-72
references.pmid: 8920992
references.citation: Am J Pathol. 1925 Jan;1(1):77-90.15
references.pmid: 19969634
references.citation: J Biol Chem. 1997 Oct 3;272(40):25083-90
references.pmid: 9312117
references.citation: J Neurosci Res. 2009 May 15;87(7):1547-55
references.pmid: 19125409
references.citation: Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):3936-41
references.pmid: 15741272
references.citation: Cancer Res. 1998 May 1;58(9):2020-8
references.pmid: 9581848
references.citation: Mol Immunol. 2010 Nov-Dec;48(1-3):82-8
references.pmid: 20956019
references.citation: Curr Opin Investig Drugs. 2010 Nov;11(11):1286-94
references.pmid: 21157648
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5809-14
references.pmid: 18359850
references.citation: J Immunol. 2000 Feb 1;164(3):1211-5
references.pmid: 10640732
references.citation: Cytokine. 2003 Dec 21;24(6):293-303
references.pmid: 14609571
references.citation: J Immunol. 2008 Jan 1;180(1):522-9
references.pmid: 18097054
references.citation: Invest Ophthalmol Vis Sci. 2008 May;49(5):1797-808
references.pmid: 18436814
references.citation: J Biol Chem. 2001 May 4;276(18):15185-91
references.pmid: 11278629
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3055-60
references.pmid: 17360608
references.citation: Neuro Oncol. 2012 Aug;14(8):958-78
references.pmid: 22573310
references.citation: J Immunol. 2003 Apr 1;170(7):3835-42
references.pmid: 12646651
references.citation: J Biol Chem. 1998 Dec 18;273(51):33893-6
references.pmid: 9852037
references.citation: J Immunol. 2002 Oct 15;169(8):4417-22
references.pmid: 12370375