title: Macrophages as mediators of tumor immunosurveillance.
abstract: Tumor immunosurveillance is a well-established mechanism for regulation of tumor growth. In this regard, most studies have focused on the role of T- and NK-cells as the critical immune effector cells. However, macrophages play a major role in the recognition and clearance of foreign, aged, and damaged cells. Macrophage phagocytosis is negatively regulated via the receptor SIRPalpha upon binding to CD47, a ubiquitously expressed protein. We recently showed that CD47 is up-regulated in myeloid leukemia and migrating hematopoietic progenitors, and that the level of protein expression correlates with the ability to evade phagocytosis. These results implicate macrophages in the immunosurveillance of hematopoietic cells and leukemias. The ability of macrophages to phagocytose tumor cells might be exploited therapeutically by blocking the CD47-SIRPalpha interaction.
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, and Ludwig Center at Stanford, USA. sjaiswal@stanford.edu
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Jaiswal
authors.forename: Mark P
authors.initials: MP
authors.lastname: Chao
authors.forename: Ravindra
authors.initials: R
authors.lastname: Majeti
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
mesh_terms: D000818:Animals; D051928:CD47 Antigen / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D009369:Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis; D015398:Signal Transduction
chemical_list: D051928:CD47 Antigen
references.citation: Nat Med. 2007 Jan;13(1):54-61
references.pmid: 17187072
references.citation: J Exp Med. 2007 Oct 29;204(11):2719-31
references.pmid: 17954568
references.citation: Cell Stem Cell. 2007 Oct 11;1(4):371-81
references.pmid: 18371376
references.citation: Trends Immunol. 2008 Oct;29(10):464-8
references.pmid: 18775673
references.citation: Cell. 2009 Jul 23;138(2):271-85
references.pmid: 19632178
references.citation: Cell Death Differ. 2007 Oct;14(10):1848-50
references.pmid: 17657249
references.citation: J Cell Biol. 2008 Mar 10;180(5):989-1003
references.pmid: 18332220
references.citation: J Exp Med. 2001 Aug 20;194(4):541-9
references.pmid: 11514609
references.citation: Cell Stem Cell. 2009 Jun 5;4(6):499-502
references.pmid: 19497277
references.citation: Semin Cancer Biol. 2004 Jun;14(3):155-60
references.pmid: 15246050
references.citation: Ann N Y Acad Sci. 2009 Sep;1174:118-21
references.pmid: 19769744
references.citation: JAMA. 2005 Sep 21;294(11):1359-66
references.pmid: 16174694
references.citation: J Exp Med. 1994 Mar 1;179(3):1047-52
references.pmid: 8113673
references.citation: Blood. 2002 Dec 15;100(13):4660-7
references.pmid: 12393415
references.citation: Leuk Res. 2005 Apr;29(4):445-50
references.pmid: 15725479
references.citation: Cell Stem Cell. 2009 Sep 4;5(3):310-9
references.pmid: 19733542
references.citation: Transfusion. 2007 Sep;47(9):1725-32
references.pmid: 17725740
references.citation: Front Biosci. 2007 May 01;12:4298-314
references.pmid: 17485376
references.citation: Science. 2000 Jun 16;288(5473):2051-4
references.pmid: 10856220
references.citation: Nat Immunol. 2007 Dec;8(12):1313-23
references.pmid: 17982459
references.citation: J Cancer Res Clin Oncol. 1982;103(1):31-8
references.pmid: 7076715
references.citation: Oncol Rep. 2007 May;17(5):1189-94
references.pmid: 17390064
references.citation: Hepatology. 1995 Feb;21(2):487-94
references.pmid: 7843723
references.citation: J Biol Chem. 1999 Jan 8;274(2):559-62
references.pmid: 9872987
references.citation: Nature. 2001 Sep 13;413(6852):165-71
references.pmid: 11557981
references.citation: Annu Rev Immunol. 2002;20:825-52
references.pmid: 11861619
references.citation: Cancer Immunol Immunother. 2005 Mar;54(3):187-207
references.pmid: 15309328
references.citation: Leuk Lymphoma. 2005 Dec;46(12):1775-84
references.pmid: 16263581
references.citation: Mol Biol Cell. 2004 Aug;15(8):3950-63
references.pmid: 15215311
references.citation: J Clin Oncol. 2005 Dec 10;23(35):8959-67
references.pmid: 16219934
references.citation: Nat Rev Immunol. 2006 Jun;6(6):457-64
references.pmid: 16691243
references.citation: J Lipid Res. 2005 Jan;46(1):11-20
references.pmid: 15548472
references.citation: Nat Rev Immunol. 2006 Nov;6(11):836-48
references.pmid: 17063185
references.citation: J Cell Sci. 1995 Nov;108 ( Pt 11):3419-25
references.pmid: 8586654
references.citation: Drugs. 2002;62 Suppl 1:1-15
references.pmid: 12479591
references.citation: J Immunol. 2000 Feb 15;164(4):2193-9
references.pmid: 10657674
references.citation: Crit Rev Oncol Hematol. 2002 Nov;44(2):143-61
references.pmid: 12413632
references.citation: Cancer Res. 1987 Dec 15;47(24 Pt 1):6686-91
references.pmid: 3119198
references.citation: Nat Rev Immunol. 2003 Jan;3(1):23-35
references.pmid: 12511873
references.citation: Lancet. 2006 Nov 25;368(9550):1894-907
references.pmid: 17126723
references.citation: Semin Cancer Biol. 2008 Oct;18(5):349-55
references.pmid: 18467122
references.citation: Crit Rev Oncol Hematol. 2008 Apr;66(1):1-9
references.pmid: 17913510
references.citation: Cell. 1990 Jun 1;61(5):759-67
references.pmid: 2188735
references.citation: Hepatology. 1996 May;23(5):1224-31
references.pmid: 8621157
references.citation: Nat Med. 1999 Nov;5(11):1277-84
references.pmid: 10545994
references.citation: J Immunol. 2007 Feb 15;178(4):1975-9
references.pmid: 17277099
references.citation: J Infect Dis. 2005 Nov 1;192(9):1666-71
references.pmid: 16206084
references.citation: Carcinogenesis. 2009 Jul;30(7):1073-81
references.pmid: 19468060
references.citation: Nature. 2002 Jul 11;418(6894):200-3
references.pmid: 12110892
references.citation: Mol Immunol. 2004 Nov;41(11):1109-21
references.pmid: 15476922
references.citation: Nature. 1986 Feb 20-26;319(6055):675-8
references.pmid: 3951539
references.citation: Science. 2001 Nov 30;294(5548):1933-6
references.pmid: 11729320
references.citation: Cancer Res. 1992 Oct 1;52(19):5416-20
references.pmid: 1394148
references.citation: Biochem Biophys Res Commun. 2004 Mar 19;315(4):912-8
references.pmid: 14985099
references.citation: J Exp Med. 1997 Jan 6;185(1):1-11
references.pmid: 8996237
references.citation: Tumour Biol. 2008;29(1):28-34
references.pmid: 18497546
references.citation: Science. 1999 Jul 30;285(5428):727-9
references.pmid: 10426993
references.citation: Hepatology. 1991 Aug;14(2):318-24
references.pmid: 1907256
references.citation: J Clin Invest. 2001 Oct;108(7):957-62
references.pmid: 11581295
references.citation: Nature. 2005 Aug 25;436(7054):1186-90
references.pmid: 15995699
references.citation: Am J Pathol. 2008 Oct;173(4):1100-12
references.pmid: 18787106
references.citation: Br Med J. 1957 Apr 13;1(5023):841-7
references.pmid: 13413231
references.citation: J Biol Chem. 2001 Oct 26;276(43):40156-66
references.pmid: 11479293
references.citation: Nature. 2007 Nov 15;450(7168):435-9
references.pmid: 17960135
references.citation: Trends Cell Biol. 2001 Mar;11(3):130-5
references.pmid: 11306274
references.citation: EMBO J. 2006 Nov 29;25(23):5560-8
references.pmid: 17093498
references.citation: Nature. 2001 Nov 1;414(6859):105-11
references.pmid: 11689955
references.citation: J Clin Invest. 1992 Oct;90(4):1513-22
references.pmid: 1383273
references.citation: Science. 1996 Nov 1;274(5288):795-8
references.pmid: 8864123
references.citation: Cell. 2000 Jan 7;100(1):57-70
references.pmid: 10647931
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):14016-21
references.pmid: 19666525
references.citation: Cell. 2005 Oct 21;123(2):321-34
references.pmid: 16239148
references.citation: Blood. 1993 Jun 15;81(12):3474-9
references.pmid: 8507882
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5062-6
references.pmid: 17360380
references.citation: Cell. 2009 Jul 23;138(2):286-99
references.pmid: 19632179
references.citation: Blood. 2002 Oct 15;100(8):2882-90
references.pmid: 12351399
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11784-9
references.pmid: 18689689
references.citation: J Biol Chem. 1996 Jan 5;271(1):21-4
references.pmid: 8550562
references.citation: J Immunol. 2004 Aug 15;173(4):2562-70
references.pmid: 15294972
references.citation: Trends Immunol. 2008 May;29(5):203-6
references.pmid: 18394962
references.citation: Nat Rev Immunol. 2009 Aug;9(8):568-80
references.pmid: 19629084
references.citation: Gynecol Oncol. 2007 Jul;106(1):160-3
references.pmid: 17490737
references.citation: Oncol Rep. 2003 Mar-Apr;10(2):309-13
references.pmid: 12579264
references.citation: Blood. 2001 May 1;97(9):2741-9
references.pmid: 11313266