title: Control of the adaptive immune response by tumor vasculature.
abstract: THE ENDOTHELIUM IS NOWADAYS DESCRIBED AS AN ENTIRE ORGAN THAT REGULATES VARIOUS PROCESSES: vascular tone, coagulation, inflammation, and immune cell trafficking, depending on the vascular site and its specific microenvironment as well as on endothelial cell-intrinsic mechanisms like epigenetic changes. In this review, we will focus on the control of the adaptive immune response by the tumor vasculature. In physiological conditions, the endothelium acts as a barrier regulating cell trafficking by specific expression of adhesion molecules enabling adhesion of immune cells on the vessel, and subsequent extravasation. This process is also dependent on chemokine and integrin expression, and on the type of junctions defining the permeability of the endothelium. Endothelial cells can also regulate immune cell activation. In fact, the endothelial layer can constitute immunological synapses due to its close interactions with immune cells, and the delivery of co-stimulatory or co-inhibitory signals. In tumor conditions, the vasculature is characterized by an abnormal vessel structure and permeability, and by a specific phenotype of endothelial cells. All these abnormalities lead to a modulation of intra-tumoral immune responses and contribute to the development of intra-tumoral immunosuppression, which is a major mechanism for promoting the development, progression, and treatment resistance of tumors. The in-depth analysis of these various abnormalities will help defining novel targets for the development of anti-tumoral treatments. Furthermore, eventual changes of the endothelial cell phenotype identified by plasma biomarkers could secondarily be selected to monitor treatment efficacy.
authors.affiliation: INSERM U970, PARCC (Paris Cardiovascular Research Center), Université Paris-Descartes, Sorbonne Paris Cité , Paris , France ; Service d'Hématologie Biologique, Hôpital Européen Georges Pompidou , Paris , France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Mauge
authors.affiliation: INSERM U970, PARCC (Paris Cardiovascular Research Center), Université Paris-Descartes, Sorbonne Paris Cité , Paris , France.
authors.forename: Magali
authors.initials: M
authors.lastname: Terme
authors.affiliation: INSERM U970, PARCC (Paris Cardiovascular Research Center), Université Paris-Descartes, Sorbonne Paris Cité , Paris , France ; Service d'Immunologie Biologique, Hôpital Européen Georges Pompidou , Paris , France.
authors.forename: Eric
authors.initials: E
authors.lastname: Tartour
authors.affiliation: INSERM U970, PARCC (Paris Cardiovascular Research Center), Université Paris-Descartes, Sorbonne Paris Cité , Paris , France ; Service d'Hématologie Biologique, Hôpital Européen Georges Pompidou , Paris , France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Helley
keywords: adaptive immunity; endothelial cell; immunological synapse; lymphocyte infiltration; tumor
references.citation: Clin Dev Immunol. 2010;2010:683875
references.pmid: 21127709
references.citation: J Clin Oncol. 2007 Mar 1;25(7):852-61
references.pmid: 17327606
references.citation: Mod Pathol. 2010 Aug;23(8):1104-12
references.pmid: 20495537
references.citation: Blood. 2011 Nov 3;118(18):4853-62
references.pmid: 21908423
references.citation: J Thromb Haemost. 2005 Jul;3(7):1392-406
references.pmid: 15892866
references.citation: Blood. 2010 May 6;115(18):3843-51
references.pmid: 20185588
references.citation: Am J Pathol. 2004 Aug;165(2):601-8
references.pmid: 15277233
references.citation: Clin Cancer Res. 2001 Mar;7(3):524-32
references.pmid: 11297243
references.citation: Int J Cancer. 2004 May 20;110(1):51-60
references.pmid: 15054868
references.citation: Blood. 2006 Oct 1;108(7):2339-48
references.pmid: 16794251
references.citation: Cancer Metastasis Rev. 2011 Mar;30(1):83-95
references.pmid: 21249423
references.citation: Cancer Res. 2009 Mar 1;69(5):2000-9
references.pmid: 19244125
references.citation: Science. 2000 Aug 18;289(5482):1197-202
references.pmid: 10947988
references.citation: J Immunol. 2007 Nov 15;179(10):6673-85
references.pmid: 17982057
references.citation: Gastroenterology. 1996 Apr;110(4):1175-81
references.pmid: 8613007
references.citation: J Clin Invest. 2007 May;117(5):1147-54
references.pmid: 17476344
references.citation: Hepatology. 2010 Jun;51(6):2172-82
references.pmid: 20513002
references.citation: Nature. 2008 May 15;453(7193):410-4
references.pmid: 18418378
references.citation: Immunol Res. 2004;29(1-3):197-208
references.pmid: 15181282
references.citation: Nat Rev Drug Discov. 2011 Jun;10(6):417-27
references.pmid: 21629292
references.citation: Nat Med. 1998 Apr;4(4):415-20
references.pmid: 9546786
references.citation: Blood. 2013 Jan 10;121(2):403-15
references.pmid: 23074273
references.citation: Cell. 2011 Mar 4;144(5):646-74
references.pmid: 21376230
references.citation: Cancer Res. 2013 Jan 15;73(2):539-49
references.pmid: 23108136
references.citation: Br J Cancer. 2010 Oct 12;103(8):1245-54
references.pmid: 20877351
references.citation: Hypertension. 1998 Jul;32(1):89-95
references.pmid: 9674643
references.citation: Cancer Res. 2011 Feb 1;71(3):801-11
references.pmid: 21266358
references.citation: Oncology. 2010;79(3-4):187-96
references.pmid: 21358206
references.citation: Cancer Res. 1999 Aug 1;59(15):3698-704
references.pmid: 10446984
references.citation: Cancer Cell. 2004 Dec;6(6):553-63
references.pmid: 15607960
references.citation: Circ Res. 2006 Feb 3;98(2):159-62
references.pmid: 16456105
references.citation: Eur J Immunol. 2003 Nov;33(11):3117-26
references.pmid: 14579280
references.citation: Am J Pathol. 2000 Nov;157(5):1703-11
references.pmid: 11073829
references.citation: Blood Rev. 2010 Nov;24(6):203-19
references.pmid: 20870325
references.citation: Biochim Biophys Acta. 2009 Oct;1792(10):954-73
references.pmid: 19607914
references.citation: Cancer Immunol Immunother. 2008 Jul;57(7):951-61
references.pmid: 18058097
references.citation: Cancer Res. 2013 Mar 1;73(5):1547-58
references.pmid: 23436794
references.citation: Blood. 2003 Apr 1;101(7):2620-7
references.pmid: 12411307
references.citation: Cancer Res. 2011 Oct 15;71(20):6391-9
references.pmid: 21900403
references.citation: Am J Pathol. 2006 Feb;168(2):706-13
references.pmid: 16436683
references.citation: Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19461-6
references.pmid: 20978210
references.citation: Hepatology. 2009 Dec;50(6):1839-50
references.pmid: 19824075
references.citation: Trends Immunol. 2011 Dec;32(12):603-11
references.pmid: 21958759
references.citation: Cancer Res. 2012 May 1;72(9):2162-71
references.pmid: 22549946
references.citation: Clin Cancer Res. 2006 Nov 15;12(22):6808-16
references.pmid: 17121902
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17174-9
references.pmid: 15569934
references.citation: Immunity. 2012 Mar 23;36(3):362-73
references.pmid: 22406269
references.citation: Hum Immunol. 2009 Jun;70(6):375-82
references.pmid: 19480853
references.citation: Cancer Res. 2008 Sep 15;68(18):7264-9
references.pmid: 18794112
references.citation: Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2891-6
references.pmid: 21282653
references.citation: Nat Rev Immunol. 2009 Mar;9(3):162-74
references.pmid: 19197294
references.citation: Cancer Immunol Immunother. 2010 Feb;59(2):267-77
references.pmid: 19669642
references.citation: J Exp Med. 2010 Mar 15;207(3):505-20
references.pmid: 20176801
references.citation: Clin Cancer Res. 2014 Apr 15;20(8):2147-58
references.pmid: 24523438
references.citation: Clin Dev Immunol. 2012;2012:492920
references.pmid: 23320019
references.citation: Blood. 1996 Jul 15;88(2):667-73
references.pmid: 8695814
references.citation: Annu Rev Physiol. 1995;57:827-72
references.pmid: 7778885
references.citation: Int J Cancer. 2000 Mar 20;89(2):122-6
references.pmid: 10754488
references.citation: Cancer Res. 2010 Aug 1;70(15):6171-80
references.pmid: 20631075
references.citation: Gynecol Oncol. 2012 Jan;124(1):105-11
references.pmid: 21982044
references.citation: Int J Biochem Cell Biol. 2009 Nov;41(11):2163-72
references.pmid: 19782948
references.citation: Mol Imaging Biol. 2009 Nov-Dec;11(6):460-6
references.pmid: 19434461
references.citation: Clin Cancer Res. 2008 Oct 15;14(20):6674-82
references.pmid: 18927310
references.citation: J Immunol. 2007 Feb 1;178(3):1505-11
references.pmid: 17237399
references.citation: Cancer Res. 2004 Nov 15;64(22):8411-9
references.pmid: 15548712
references.citation: Oncogene. 2014 Mar 27;33(13):1725-35
references.pmid: 23584483
references.citation: Cancer Immunol Immunother. 2008 Aug;57(8):1115-24
references.pmid: 18193223
references.citation: Ann N Y Acad Sci. 2001 Sep;941:12-25
references.pmid: 11594565
references.citation: Immunity. 2013 Jul 25;39(1):61-73
references.pmid: 23890064
references.citation: Hepatology. 2008 Jan;47(1):296-305
references.pmid: 17975811
references.citation: Nature. 2011 Jul 13;475(7355):226-30
references.pmid: 21753853
references.citation: J Cancer Res Clin Oncol. 2010 Nov;136(11):1737-43
references.pmid: 20213100
references.citation: J Immunol. 2011 Apr 1;186(7):4147-55
references.pmid: 21368224
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10623-8
references.pmid: 12963823
references.citation: BJU Int. 2011 Feb;107(4):562-70
references.pmid: 20840548
references.citation: Clin Cancer Res. 2009 Mar 15;15(6):2148-57
references.pmid: 19276286
references.citation: Nat Med. 2013 Jan;19(1):57-64
references.pmid: 23202296
references.citation: Microcirculation. 2002 Apr;9(2):133-45
references.pmid: 11932780
references.citation: Nat Rev Immunol. 2007 Oct;7(10):803-15
references.pmid: 17893694
references.citation: J Immunother. 2010 Nov-Dec;33(9):991-8
references.pmid: 20948437
references.citation: Int J Cancer. 2014 Apr 1;134(7):1695-705
references.pmid: 24105638
references.citation: EMBO J. 2003 Nov 3;22(21):5700-11
references.pmid: 14592969
references.citation: Open Access J Urol. 2010 Aug 04;2:125-41
references.pmid: 24198621
references.citation: J Immunother. 2011 Apr;34(3):236-50
references.pmid: 21389874
references.citation: Cancer Res. 2011 Dec 1;71(23):7176-86
references.pmid: 22037871
references.citation: Nat Med. 2004 Sep;10(9):942-9
references.pmid: 15322536
references.citation: J Natl Cancer Inst. 2007 Aug 1;99(15):1188-99
references.pmid: 17652277
references.citation: Annu Rev Immunol. 2004;22:683-709
references.pmid: 15032593
references.citation: Arterioscler Thromb Vasc Biol. 2009 May;29(5):746-53
references.pmid: 19229070
references.citation: Clin Cancer Res. 2008 Aug 15;14(16):5150-7
references.pmid: 18694993
references.citation: J Immunol. 2009 Mar 1;182(5):2654-64
references.pmid: 19234159
references.citation: Int J Cancer. 2012 Apr 15;130(8):1948-59
references.pmid: 21633954
references.citation: Nat Med. 2008 Jan;14(1):28-36
references.pmid: 18157142
references.citation: Nat Rev Cancer. 2012 Mar 15;12(4):298-306
references.pmid: 22419253
references.citation: Cancer Cell. 2007 Jun;11(6):539-54
references.pmid: 17560335
references.citation: J Neurooncol. 2003 Aug-Sep;64(1-2):55-61
references.pmid: 12952286
references.citation: J Exp Med. 1990 May 1;171(5):1453-67
references.pmid: 1692079
references.citation: Hepatology. 2012 Nov;56(5):1924-33
references.pmid: 22610745
references.citation: Nat Med. 1997 Jun;3(6):682-5
references.pmid: 9176498
references.citation: Cancer Res. 2013 Jan 1;73(1):128-38
references.pmid: 23135914
references.citation: J Transl Med. 2012 Jan 03;10:1
references.pmid: 22214470
references.citation: Blood. 2003 Jul 1;102(1):184-91
references.pmid: 12609848
references.citation: Am J Clin Pathol. 2001 Apr;115(4):543-9
references.pmid: 11293902
references.citation: Annu Rev Pathol. 2011;6:323-44
references.pmid: 21073340
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10391-10396
references.pmid: 16798883
references.citation: Cell. 2009 Mar 6;136(5):839-851
references.pmid: 19217150
references.citation: Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4651-5
references.pmid: 1675786
references.citation: Immunol Res. 1999;19(2-3):225-32
references.pmid: 10493176
references.citation: Nature. 2004 Apr 15;428(6984):754-8
references.pmid: 15085134
references.citation: Nat Med. 1996 Oct;2(10):1096-103
references.pmid: 8837607
references.citation: Int J Cancer. 2011 Nov 1;129(9):2158-70
references.pmid: 21170961
references.citation: Blood. 2002 Mar 15;99(6):2114-21
references.pmid: 11877287
references.citation: Nat Rev Immunol. 2006 Oct;6(10):715-27
references.pmid: 16977338
references.citation: Cell. 2010 Mar 19;140(6):883-99
references.pmid: 20303878
references.citation: Nat Rev Cancer. 2003 Feb;3(2):110-6
references.pmid: 12563310
references.citation: Blood. 1998 May 15;91(10):3527-61
references.pmid: 9572988
references.citation: Trends Immunol. 2012 Jan;33(1):49-57
references.pmid: 22030237
references.citation: Nat Med. 2013 Sep;19(9):1114-23
references.pmid: 23913124
references.citation: Clin Cancer Res. 2007 Dec 1;13(23):6993-7002
references.pmid: 18056175
references.citation: Microvasc Res. 2011 May;81(3):261-8
references.pmid: 21277871
references.citation: J Biol Chem. 2002 Aug 2;277(31):27850-5
references.pmid: 12023962
references.citation: J Immunol. 2012 Mar 15;188(6):2687-94
references.pmid: 22323546
references.citation: Cancer Res. 2011 Sep 1;71(17):5678-87
references.pmid: 21846823
references.citation: J Mol Med (Berl). 2013 Jul;91(7):883-99
references.pmid: 23471434