title: Tumor-infiltrating immune cells promoting tumor invasion and metastasis: existing theories.
abstract: It is a commonly held belief that infiltration of immune cells into tumor tissues and direct physical contact between tumor cells and infiltrated immune cells is associated with physical destructions of the tumor cells, reduction of the tumor burden, and improved clinical prognosis. An increasing number of studies, however, have suggested that aberrant infiltration of immune cells into tumor or normal tissues may promote tumor progression, invasion, and metastasis. Neither the primary reason for these contradictory observations, nor the mechanism for the reported diverse impact of tumor-infiltrating immune cells has been elucidated, making it difficult to judge the clinical implications of infiltration of immune cells within tumor tissues. This mini-review presents several existing hypotheses and models that favor the promoting impact of tumor-infiltrating immune cells on tumor invasion and metastasis, and also analyzes their strength and weakness.
authors: 1. Diagnostic and Translational Research Center, Henry Jackson Foundation, Gaithersburg, MD, USA; ; 2. College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin, China;
authors: Yan-Gao
authors: YG
authors: Man
authors: Alexander
authors: A
authors: Stojadinovic
authors: Jeffrey
authors: J
authors: Mason
authors: Itzhak
authors: I
authors: Avital
authors: Anton
authors: A
authors: Bilchik
authors: Bjoern
authors: B
authors: Bruecher
authors: Mladjan
authors: M
authors: Protic
authors: Aviram
authors: A
authors: Nissan
authors: Mina
authors: M
authors: Izadjoo
authors: Xichen
authors: X
authors: Zhang
authors: Anahid
authors: A
authors: Jewett
keywords: immune cell; invasion; metastasis; tumor progression
references: Biochem Biophys Res Commun. 2011 Nov 11;415(1):187-92
references: 22033416
references: Cancer Sci. 2004 Mar;95(3):260-5
references: 15016327
references: Lab Invest. 1999 Dec;79(12):1629-42
references: 10616212
references: Cell Transplant. 2013;22(10):1869-82
references: 23067574
references: Biochem Pharmacol. 2004 Sep 15;68(6):1033-40
references: 15313398
references: J Radiol Prot. 2002 Sep;22(3A):A43-9
references: 12400946
references: Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):1994-2003
references: 16609008
references: Cancer Biomark. 2010;9(1-6):325-39
references: 22112483
references: Clin Immunol. 2011 Jan;138(1):23-32
references: 21041120
references: Cancer Epidemiol. 2010 Feb;34(1):3-6
references: 20022838
references: J Cell Physiol. 2001 Nov;189(2):189-96
references: 11598904
references: Med Hypotheses. 2008;70(2):387-408
references: 17658698
references: Curr Drug Deliv. 2012 Jan;9(1):5-16
references: 22023212
references: Int J Biol Sci. 2009;5(3):276-85
references: 19343113
references: J Pathol. 1999 Oct;189(2):161-8
references: 10547569
references: N Engl J Med. 2003 Jan 16;348(3):203-13
references: 12529460
references: Int J Cancer. 1993 Jan 21;53(2):269-77
references: 8425764
references: Genes Chromosomes Cancer. 2003 Dec;38(4):302-6
references: 14566848
references: Int J Oncol. 2012 Apr;40(4):1285-90
references: 22200673
references: J Biomed Biotechnol. 2010;2010:901564
references: 20445748
references: Oncoimmunology. 2012 Aug 1;1(5):717-725
references: 22934263
references: J Urol. 2006 Sep;176(3):1012-6
references: 16890681
references: FASEB J. 1996 Sep;10(11):1280-9
references: 8836041
references: J Biol Chem. 1994 Dec 9;269(49):30988-93
references: 7983035
references: Methods Mol Biol. 2006;315:257-72
references: 16273706
references: Cancer. 2010 Feb 1;116(3):544-73
references: 19998273
references: Oncologist. 2007 Apr;12(4):418-25
references: 17470684
references: J Leukoc Biol. 2008 Sep;84(3):623-30
references: 18467655
references: Future Oncol. 2008 Aug;4(4):449-52
references: 18684055
references: Lancet Oncol. 2012 May;13(5):518-27
references: 22440112
references: J Leukoc Biol. 2000 Dec;68(6):785-92
references: 11129645
references: Cancer Res. 1991 Aug 15;51(16):4257-65
references: 1868446
references: Adv Exp Med Biol. 2011;714:151-72
references: 21506013
references: Science. 1994 Jan 28;263(5146):526-9
references: 8290962
references: J Cell Biochem. 2011 Apr;112(4):1154-67
references: 21312236
references: Clin Cancer Res. 2001 Sep;7(9):2682-92
references: 11555580
references: Nat Rev Cancer. 2008 May;8(5):377-86
references: 18385683
references: PLoS One. 2012;7(9):e46391
references: 23050024
references: J Immunol. 2004 Mar 1;172(5):2731-8
references: 14978070
references: Int J Cancer. 2011 Jun 1;128(11):2536-44
references: 21387299
references: J Biol Chem. 2012 Jul 20;287(30):25353-60
references: 22573321
references: J Biol Chem. 1989 Nov 25;264(33):19654-8
references: 2584186
references: Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19093-6
references: 16361440
references: Cancer. 1994 Aug 15;74(4):1275-82
references: 7914469
references: Science. 2002 Mar 29;295(5564):2387-92
references: 11923519
references: Oncol Res. 1996;8(2):69-75
references: 8859777
references: Immunol Today. 1997 Jun;18(6):267-8
references: 9190110
references: Cancer Metastasis Rev. 2008 Mar;27(1):11-8
references: 18066650
references: Prostate. 1994;24(3):114-8
references: 7509483
references: Lancet Oncol. 2005 Dec;6(12):988-93
references: 16321767
references: Clin Cancer Res. 1995 Oct;1(10):1089-94
references: 9815898
references: Cell Mol Life Sci. 2001 Jul;58(8):1150-8
references: 11529507
references: Gynecol Oncol. 2004 Jan;92(1):47-56
references: 14751137
references: Nature. 2006 May 25;441(7092):444-50
references: 16724056
references: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references: 21296855
references: Cancer Res. 2007 Mar 15;67(6):2649-56
references: 17363585
references: J Cancer. 2010 Jun 02;1:32-7
references: 20842222
references: J Immunol. 2003 Sep 1;171(5):2187-91
references: 12928361
references: Blood. 2003 Aug 1;102(3):881-6
references: 12676789
references: Cell Adh Migr. 2007 Jan-Mar;1(1):2-6
references: 19262091
references: Semin Thromb Hemost. 1986 Oct;12(4):294-307
references: 3024322
references: J Immunol. 1989 May 15;142(10):3714-25
references: 2785562
references: J Natl Cancer Inst. 1996 Aug 21;88(16):1146-51
references: 8757194
references: Cancer Res. 2010 Oct 1;70(19):7465-75
references: 20841473
references: Nat Rev Cancer. 2006 Apr;6(4):281-91
references: 16557280
references: J Cancer. 2010 Jun 24;1:63-9
references: 20842226
references: Breast Cancer Res. 2006;8(2):R18
references: 16584539
references: Oncogene. 2013 Jul 25;32(30):3500-9
references: 22945654
references: J Surg Oncol. 2009 Nov 1;100(6):500-4
references: 19697355
references: Oral Oncol. 2012 Nov;48(11):1068-75
references: 22766510
references: Nature. 2011 Jul 13;475(7355):226-30
references: 21753853
references: Am J Clin Pathol. 2005 Dec;124 Suppl:S16-28
references: 16468415
references: Breast Cancer Res. 2003;5(6):R231-41
references: 14580259
references: Appl Immunohistochem Mol Morphol. 2005 Mar;13(1):30-7
references: 15722791
references: Cell. 2004 Aug 6;118(3):277-9
references: 15294153
references: Cancer Immunol Immunother. 2008 Jul;57(7):1053-66
references: 18188563
references: Curr Opin Genet Dev. 2008 Feb;18(1):27-34
references: 18282701
references: J Leukoc Biol. 2007 Mar;81(3):579
references: 29350850
references: Clin Cancer Res. 2007 Jul 1;13(13):3951-9
references: 17606729
references: J Cancer. 2011;2:443-57
references: 21850212
references: Prog Clin Biol Res. 1987;239:317-25
references: 3658984
references: Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4622-6
references: 16303958
references: Gynecol Oncol. 2003 May;89(2):271-80
references: 12713991
references: Gut. 1999 Feb;44(2):156-62
references: 9895372
references: J Surg Res. 1999 Jan;81(1):42-7
references: 9889056
references: Int J Biol Sci. 2008 Aug 16;4(5):259-69
references: 18726004
references: Med Hypotheses. 2007;69(6):1340-57
references: 17493765
references: J Exp Med. 2005 Mar 7;201(5):779-91
references: 15753211
references: Nat Med. 2004 Sep;10(9):942-9
references: 15322536
references: Int Immunopharmacol. 2011 Jul;11(7):856-61
references: 21315783
references: Eur J Biochem. 1993 Apr 15;213(2):833-9
references: 7682948
references: Science. 1991 Dec 13;254(5038):1643-7
references: 1840703
references: Vet Pathol. 2002 Mar;39(2):190-9
references: 12009057
references: PLoS One. 2012;7(9):e44728
references: 23028594
references: Immunology. 1991 Sep;74(1):153-9
references: 1937568
references: Nat Immunol. 2002 Feb;3(2):102
references: 11812978
references: Adv Cancer Res. 2008;101:397-444
references: 19055949
references: Eur Urol. 1996;30(2):201-5
references: 8875201
references: Semin Diagn Pathol. 1994 Aug;11(3):223-35
references: 7831534
references: Hepatology. 2000 Sep;32(3):491-500
references: 10960440
references: Pediatr Nephrol. 1999 Oct;13(8):709-15
references: 10502132
references: Crit Rev Eukaryot Gene Expr. 1995;5(1):1-77
references: 7549180
references: Breast Cancer Res. 2000;2(4):252-7
references: 11250717
references: Cancer Immunol Immunother. 1995 Oct;41(4):243-50
references: 7489567
references: N Engl J Med. 2005 Dec 22;353(25):2654-66
references: 16371631
references: Int J Biol Sci. 2010 Mar 09;6(2):129-32
references: 20224734
references: J Biol Chem. 2006 Jan 6;281(1):626-37
references: 16253990
references: Med Sci Monit. 2006 Mar;12(3):RA53-6
references: 16501434
references: Immunology. 2009 Sep;128(1):7-15
references: 19689731
references: Exp Biol Med (Maywood). 2011 May 1;236(5):567-79
references: 21486861
references: PLoS One. 2010 Jul 16;5(7):e11590
references: 20661281
references: Cancer Immunol Immunother. 2012 Feb;61(2):265-274
references: 22116348
references: Anticancer Drugs. 2005 Sep;16(8):855-61
references: 16096433
references: J Reprod Immunol. 2012 Jun;94(2):131-41
references: 22542910
references: J Immunol. 2006 May 1;176(9):5519-28
references: 16622021
references: Semin Cancer Biol. 2008 Oct;18(5):322-9
references: 18456510
references: PLoS One. 2012;7(9):e45590
references: 23029122
references: Anticancer Res. 1999 Mar-Apr;19(2C):1589-92
references: 10365151
references: J Cell Physiol. 2004 Nov;201(2):266-76
references: 15334661
references: Immunotherapy. 2009 Sep;1(5):753-64
references: 20636021
references: Cancer Epidemiol. 2011 Oct;35(5):475-9
references: 21292584
references: Toxicology. 2003 Jun 3;188(1):49-71
references: 12748041
references: Nat Rev Immunol. 2010 Dec;10(12):849-59
references: 21107346
references: Cold Spring Harb Perspect Biol. 2011 Mar 01;3(3):
references: 21123394
references: Nat Rev Immunol. 2010 Aug;10(8):568-79
references: 20634814
references: Cancer Res. 1995 Sep 15;55(18):4140-5
references: 7545086
references: Br J Cancer. 1998 Jul;78(1):46-9
references: 9662249
references: Mol Med. 2000 Jun;6(6):465-79
references: 10972084
references: Am J Surg Pathol. 2001 Aug;25(8):1054-60
references: 11474290
references: Neoplasma. 1988;35(6):691-705
references: 3265486
references: Cancer. 1995 Oct 1;76(7):1197-200
references: 8630897
references: Cancer Immun. 2008 Jun 12;8:10
references: 18547033
references: Anticancer Res. 1994 Nov-Dec;14(6B):2465-72
references: 7872668
references: Cancer Immunol Immunother. 2010 May;59(5):653-61
references: 19908042
references: Mediators Inflamm. 2012;2012:693083
references: 22577254
references: J Pathol. 2010 Dec;222(4):350-66
references: 20927778
references: J Pathol. 1998 Nov;186(3):240-6
references: 10211111
references: Cancer. 1982 Feb 15;49(4):751-8
references: 6275978
references: Br J Cancer. 2002 May 6;86(9):1444-8
references: 11986779
references: Cancer Immunol Immunother. 2011 Nov;60(11):1565-75
references: 21681375
references: Cancer Res. 2004 Oct 1;64(19):7022-9
references: 15466195
references: J Neurosci. 2000 Oct 1;20(19):7377-83
references: 11007896
references: Pathobiology. 1999;67(5-6):302-5
references: 10725808
references: Nat Rev Cancer. 2004 Jan;4(1):71-8
references: 14708027
references: Pathologica. 1994 Apr;86(2):128-41
references: 7524011
references: Cancer Metastasis Rev. 2010 Jun;29(2):309-16
references: 20405169
references: Veroff Pathol. 1995;145:1-139
references: 8638427
references: Breast Cancer Res Treat. 2005 Jan;89(2):199-208
references: 15692763
references: Prostate Cancer Prostatic Dis. 2003;6(4):305-10
references: 14663472
references: BMC Clin Pathol. 2003 Sep 12;3(1):3
references: 12971830
references: Expert Rev Anticancer Ther. 2009 Dec;9(12):1829-47
references: 19954294
references: Med Hypotheses. 1997 Jan;48(1):37-46
references: 9049988
references: Virchows Arch A Pathol Anat Histopathol. 1991;418(5):375-81
references: 2035251
references: Cell Death Differ. 2010 Apr;17(4):616-23
references: 20075940
references: Nat Rev Immunol. 2003 Sep;3(9):710-20
references: 12949495
references: Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10721-5
references: 15249662
references: Front Biosci (Landmark Ed). 2010 Jan 01;15(1):226-36
references: 20036817
references: Cancer Res. 2003 Oct 1;63(19):6105-9
references: 14559785
references: Cancer Detect Prev. 2005;29(2):161-9
references: 15829376