title: Clinical uses of GM-CSF, a critical appraisal and update.
abstract: The role of granulocyte-macrophage-colony-stimulating factor (GM-CSF) in the supportive care of cancer patients has been evaluated with promising results. More recently, GM-CSF has been added to regimens for the mobilization of hematopoietic progenitor cells. An expanding role for GM-CSF in regulating immune responses has been recognized based upon its activity on the development and maturation of antigen presenting cells and its capability for skewing the immune system toward Th1-type responses. GM-CSF has been shown to preferentially enhance both the numbers and activity of type 1 dendritic cells (DC1), the subsets of dendritic cells responsible for initiating cytotoxic immune responses. The increase in DC1 content and activity following local and systemic GM-CSF administration support a role for GM-CSF as an immune stimulant and vaccine adjuvant in cancer patients. GM-CSF has shown clinical activity as an immune stimulant in tumor cell and dendritic cell vaccines, and may increase antibody-dependent cellular cytotoxicity. The successful use of myeloid acting cytokines to enhance anti-tumor responses will likely require the utilization of GM-CSF in combination with cytotoxic or other targeted therapies.
authors.affiliation: Emory University, Winship Cancer Institute, Atlanta, GA, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Arellano
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
references.citation: Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13141-6
references.pmid: 9789055
references.citation: Acta Med Scand Suppl. 1953;276:1-103
references.pmid: 13039964
references.citation: J Clin Oncol. 2003 Nov 1;21(21):4016-26
references.pmid: 14581425
references.citation: Blood. 1997 Oct 15;90(8):3037-49
references.pmid: 9376584
references.citation: Blood. 2001 Apr 15;97(8):2514-21
references.pmid: 11290617
references.citation: Blood. 2001 Apr 1;97(7):1942-6
references.pmid: 11264156
references.citation: Blood. 1994 Sep 15;84(6):1737-46
references.pmid: 7521686
references.citation: Oncol Rep. 2005 Apr;13(4):751-6
references.pmid: 15756453
references.citation: Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3539-43
references.pmid: 8097319
references.citation: Exp Hematol. 1986 Mar;14(3):192-6
references.pmid: 2868909
references.citation: Eur J Immunol. 2001 Sep;31(9):2547-57
references.pmid: 11536152
references.citation: J Exp Med. 1997 Mar 17;185(6):1101-11
references.pmid: 9091583
references.citation: J Exp Med. 2003 May 5;197(9):1213-9
references.pmid: 12732663
references.citation: J Immunother. 2003 Mar-Apr;26(2):130-8
references.pmid: 12616104
references.citation: Blood. 2000 Apr 15;95(8):2484-90
references.pmid: 10753825
references.citation: J Immunol. 2007 Mar 1;178(5):2763-9
references.pmid: 17312119
references.citation: Curr Hematol Rep. 2004 Nov;3(6):406-12
references.pmid: 15496273
references.citation: Exp Hematol. 1981 Jul;9(6):684-90
references.pmid: 6114872
references.citation: Nature. 1998 Mar 19;392(6673):245-52
references.pmid: 9521319
references.citation: J Clin Oncol. 2006 Jul 1;24(19):3187-205
references.pmid: 16682719
references.citation: Cancer. 1996 Mar 15;77(6):1149-53
references.pmid: 8635137
references.citation: Science. 1994 Apr 29;264(5159):713-6
references.pmid: 8171324
references.citation: Blood. 2001 May 15;97(10):2948-56
references.pmid: 11342416
references.citation: J Clin Oncol. 2001 Jan 1;19(1):145-56
references.pmid: 11134207
references.citation: Ann Oncol. 2001 May;12(5):655-9
references.pmid: 11432624
references.citation: Clin Cancer Res. 2000 Apr;6(4):1267-72
references.pmid: 10778950
references.citation: Annu Rev Immunol. 1994;12:991-1045
references.pmid: 8011301
references.citation: Cancer Immunol Immunother. 2001 Sep;50(7):373-81
references.pmid: 11676397
references.citation: Blood. 1996 Mar 15;87(6):2195-204
references.pmid: 8630379
references.citation: J Immunol. 2004 Apr 15;172(8):4733-43
references.pmid: 15067049
references.citation: Exp Hematol. 2007 Aug;35(8):1163-71
references.pmid: 17562355
references.citation: Blood. 2002 Apr 15;99(8):2869-79
references.pmid: 11929777
references.citation: J Natl Cancer Inst. 2001 Jan 3;93(1):31-8
references.pmid: 11136839
references.citation: Biol Blood Marrow Transplant. 2007 Jan;13(1):116-23
references.pmid: 17222760
references.citation: Eur Urol. 2005 Sep;48(3):527-33
references.pmid: 16115526
references.citation: Blood. 1998 Feb 1;91(3):863-9
references.pmid: 9446646
references.citation: Cancer Res. 1999 Oct 15;59(20):5160-8
references.pmid: 10537292
references.citation: Br J Cancer. 2003 Jan 27;88(2):175-80
references.pmid: 12610499
references.citation: Eur J Immunol. 2004 Mar;34(3):796-805
references.pmid: 14991609
references.citation: Cancer Immunol Immunother. 1990;31(4):231-5
references.pmid: 2199042
references.citation: J Exp Med. 1992 Dec 1;176(6):1693-702
references.pmid: 1460426
references.citation: Br J Cancer. 2003 May 6;88(9):1346-51
references.pmid: 12778059
references.citation: J Natl Cancer Inst. 1998 Dec 16;90(24):1894-900
references.pmid: 9862627
references.citation: Eur J Cancer. 1999 Aug;35 Suppl 3:S23-4
references.pmid: 10645217
references.citation: J Immunother. 2002 Mar-Apr;25(2):97-138
references.pmid: 12074049
references.citation: Curr Top Microbiol Immunol. 2003;276:261-75
references.pmid: 12797452
references.citation: Br J Cancer. 2001 Nov 16;85(10):1467-71
references.pmid: 11720430
references.citation: Immunol Cell Biol. 1998 Oct;76(5):441-7
references.pmid: 9797465
references.citation: J Immunother. 1998 Sep;21(5):389-98
references.pmid: 9789201
references.citation: Biol Blood Marrow Transplant. 2005 Aug;11(8):627-36
references.pmid: 16041313
references.citation: J Leukoc Biol. 1992 Sep;52(3):274-81
references.pmid: 1387891
references.citation: Gene Ther. 2000 Aug;7(15):1312-6
references.pmid: 10918502
references.citation: Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5592-6
references.pmid: 8202532
references.citation: Blood. 1994 Nov 1;84(9):3054-62
references.pmid: 7949177
references.citation: Cancer Chemother Pharmacol. 2000;46 Suppl:S67-72
references.pmid: 10950151
references.citation: J Clin Oncol. 1996 Jul;14(7):2150-9
references.pmid: 8683249
references.citation: Science. 1999 Jun 11;284(5421):1835-7
references.pmid: 10364556
references.citation: J Immunother. 2001 May-Jun;24(3):257-62
references.pmid: 11394504
references.citation: Leukemia. 2002 Nov;16(11):2197-204
references.pmid: 12399962
references.citation: Cancer Res. 1997 Apr 15;57(8):1537-46
references.pmid: 9108457
references.citation: Bone Marrow Transplant. 2002 Feb;29(4):303-12
references.pmid: 11896427
references.citation: Biol Blood Marrow Transplant. 2004 Dec;10(12):848-57
references.pmid: 15570253
references.citation: Cancer Immunol Immunother. 2004 Feb;53(2):125-34
references.pmid: 14600790
references.citation: Stem Cells Dev. 2006 Apr;15(2):269-77
references.pmid: 16646673
references.citation: J Exp Med. 2002 Mar 18;195(6):695-704
references.pmid: 11901196
references.citation: Blood. 1995 Jul 15;86(2):457-62
references.pmid: 7605984
references.citation: Best Pract Res Clin Haematol. 2004 Sep;17(3):439-51
references.pmid: 15498715
references.citation: J Immunol Methods. 2000 May 26;239(1-2):95-107
references.pmid: 10821951
references.citation: Eur J Cancer. 1999 Aug;35 Suppl 3:S33-5
references.pmid: 10645220
references.citation: Oncol Rep. 2003 Jan-Feb;10(1):127-31
references.pmid: 12469157
references.citation: Drugs. 2006;66(6):791-820
references.pmid: 16706552
references.citation: Eur J Cancer. 2003 Nov;39(16):2264-72
references.pmid: 14556916
references.citation: Bone Marrow Transplant. 1998 May;21(10):995-1003
references.pmid: 9632272
references.citation: Clin Cancer Res. 1997 Dec;3(12 Pt 2):2623-9
references.pmid: 10068264
references.citation: J Exp Med. 2001 Sep 17;194(6):863-9
references.pmid: 11561001
references.citation: Cancer. 2000 Apr 15;88(8):1892-901
references.pmid: 10760767
references.citation: J Exp Med. 1998 Dec 21;188(12):2357-68
references.pmid: 9858522
references.citation: Cytokine. 2002 Apr 7;18(1):8-19
references.pmid: 12090755
references.citation: Clin Cancer Res. 1999 Jun;5(6):1289-97
references.pmid: 10389911
references.citation: Lancet. 2001 Feb 17;357(9255):539-45
references.pmid: 11229684
references.citation: Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12551-6
references.pmid: 9356487
references.citation: Cancer Biother Radiopharm. 1998 Jun;13(3):155-64
references.pmid: 10850351
references.citation: Leukemia. 1998 Jun;12(6):860-4
references.pmid: 9639411
references.citation: Leuk Res. 2005 Jul;29(7):735-8
references.pmid: 15927668
references.citation: Biol Blood Marrow Transplant. 2004 Aug;10(8):540-51
references.pmid: 15282532
references.citation: Blood. 2003 May 1;101(9):3520-6
references.pmid: 12511409
references.citation: J Clin Oncol. 2005 Dec 10;23(35):8992-9000
references.pmid: 16260693
references.citation: Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):540-9
references.pmid: 17255276
references.citation: Blood. 2004 Jun 1;103(11):4330-5
references.pmid: 14962904
references.citation: Cochrane Database Syst Rev. 2005 Jan 25;(1):CD001425
references.pmid: 15674877
references.citation: Nat Med. 1999 Oct;5(10):1171-7
references.pmid: 10502821
references.citation: Cancer Immunol Immunother. 2002 Dec;51(11-12):630-6
references.pmid: 12439608
references.citation: J Clin Invest. 1999 Feb;103(4):563-9
references.pmid: 10021465
references.citation: Blood. 2004 Jul 1;104(1):281-9
references.pmid: 15010368
references.citation: J Clin Oncol. 2003 Sep 1;21(17):3343-50
references.pmid: 12947071
references.citation: Br J Haematol. 2003 Feb;120(3):442-51
references.pmid: 12580958
references.citation: In Vivo. 2003 Jan-Feb;17(1):73-5
references.pmid: 12655794
references.citation: N Engl J Med. 2001 Jan 18;344(3):175-81
references.pmid: 11172139
references.citation: Annu Rev Immunol. 2000;18:767-811
references.pmid: 10837075
references.citation: Blood. 2001 Nov 15;98(10):2900-8
references.pmid: 11698269
references.citation: Curr Opin Immunol. 2007 Apr;19(2):217-23
references.pmid: 17306521
references.citation: Leukemia. 2000 Mar;14(3):412-8
references.pmid: 10720135
references.citation: Cytokine Growth Factor Rev. 2002 Apr;13(2):185-93
references.pmid: 11900993
references.citation: Cancer Res. 2003 Dec 15;63(24):9007-15
references.pmid: 14695219
references.citation: Cancer Immunol Immunother. 2001 Feb;49(12):641-8
references.pmid: 11258790
references.citation: J Clin Oncol. 2006 Dec 10;24(35):5601-8
references.pmid: 17158546
references.citation: Ann Oncol. 2000 Sep;11(9):1183-9
references.pmid: 11061616
references.citation: Curr Opin Oncol. 2007 Mar;19(2):121-7
references.pmid: 17272984
references.citation: J Immunother. 1999 Mar;22(2):166-74
references.pmid: 10093041
references.citation: J Clin Oncol. 2003 Feb 15;21(4):624-30
references.pmid: 12586798
references.citation: Med Hypotheses. 2002 Feb;58(2):115-9
references.pmid: 11812185
references.citation: Leuk Res. 2001 Jan;25(1):99-100
references.pmid: 11203684
references.citation: Science. 1999 Feb 19;283(5405):1183-6
references.pmid: 10024247
references.citation: Urol Oncol. 2006 Sep-Oct;24(5):419-24
references.pmid: 16962494
references.citation: Leuk Res. 2000 May;24(5):411-5
references.pmid: 10785263
references.citation: Exp Hematol. 2003 Oct;31(10):959-65
references.pmid: 14550812
references.citation: Cancer. 2000 Mar 15;88(6):1317-24
references.pmid: 10717612
references.citation: J Immunother. 2000 Jan;23(1):48-58
references.pmid: 10687137
references.citation: J Clin Oncol. 2004 Feb 1;22(3):416-23
references.pmid: 14691124
references.citation: Cancer Immunol Immunother. 2001 Jan;49(11):613-20
references.pmid: 11225992
references.citation: Nat Med. 1996 Jan;2(1):52-8
references.pmid: 8564842
references.citation: Blood. 1997 Nov 1;90(9):3245-87
references.pmid: 9345009
references.citation: Blood. 2002 Aug 1;100(3):761-7
references.pmid: 12130483
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Nov;281(5):L1210-8
references.pmid: 11597913
references.citation: Cell. 2004 May 14;117(4):515-26
references.pmid: 15137944
references.citation: Gene. 1997 Apr 29;190(1):211-6
references.pmid: 9185869