Cancer immunotherapy: the role regulatory T cells play and what can be done to overcome their inhibitory effects.
Since multiple lines of experimental and clinical data clearly identified regulatory T cells as an integral part of the immune response, these cells have become a major focus of investigation in tumor immunology. Regulatory T cells are in place to dampen ongoing immune responses and to prevent autoimmunity, but they also have profound effects in blocking therapeutic anti-tumor activity. Therefore regulatory T cells are seen as a major hurdle that must be overcome in order for cancer immunotherapy to reach its therapeutic potential. Regulatory T cells are heterogeneous with sub-populations that exhibit distinct functional features. Here we will review the individual sub-populations in regards to their mode of action and their potential impact on blocking anti-tumor immunity. Approaches to measure function and frequency of regulatory T cells in model systems and clinical trails will be discussed. Finally, we will describe possible ways to interfere with regulatory T cell-mediated immune suppression with the focus on recent pre-clinical and clinical findings.
Petrausch
Ulf
U
Robert W. Franz Cancer Research Center, Earle. A. Chiles Research Institute, 4805 NE Glisan Street, Portland, OR 97213, USA.
Poehlein
Christian H
CH
Jensen
Shawn M
SM
Twitty
Chris
C
Thompson
James A
JA
Assmann
Ilka
I
Puri
Sachin
S
LaCelle
Michael G
MG
Moudgil
Tarsem
T
Maston
Levi
L
Friedman
Kevin
K
Church
Sarah
S
Cardenas
Elisa
E
Haley
Daniel P
DP
Walker
Edwin B
EB
Akporiaye
Emmanuel
E
Weinberg
Andrew D
AD
Rosenheim
Sidney
S
Crocenzi
Todd S
TS
Hu
Hong-Ming
HM
Curti
Brendan D
BD
Urba
Walter J
WJ
Fox
Bernard A
BA
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology; D002986:Clinical Trials as Topic; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D019496:Cancer Vaccines
J Immunol. 2007 Aug 1;179(3):1427-30
17641007
Eur Cytokine Netw. 1999 Jun;10(2):211-8
10400827
Blood. 2006 Jan 15;107(2):628-36
16179369
Microbes Infect. 2007 Sep;9(11):1325-32
17890131
Oncogene. 2005 Aug 29;24(37):5701-12
16123803
Clin Cancer Res. 2008 Mar 1;14(5):1455-63
18316569
J Exp Med. 2000 Jan 17;191(2):201-6
10637265
Mol Immunol. 2008 May;45(10):2937-50
18321576
Clin Cancer Res. 2006 Sep 15;12(18):5423-34
17000676
Science. 2006 Oct 13;314(5797):304-8
17038624
Blood. 2007 Aug 1;110(3):847-50
17412885
J Neurooncol. 2007 Jun;83(2):145-52
17216339
Clin Cancer Res. 2007 May 1;13(9):2714-21
17473204
Cancer Immunol Immunother. 2007 Sep;56(9):1429-42
17265021
Prog Exp Tumor Res. 1970;13:1-27
4921480
Science. 2002 Oct 25;298(5594):850-4
12242449
Immunity. 2007 Jul;27(1):145-59
17613255
J Immunol. 2004 May 1;172(9):5149-53
15100250
Blood. 2007 Aug 15;110(4):1225-32
17449799
J Exp Med. 2007 Jun 11;204(6):1257-65
17502665
Science. 2003 Feb 14;299(5609):1057-61
12522256
J Immunother. 2002 May-Jun;25(3):207-17
12000862
J Immunol. 2007 Mar 15;178(6):3400-8
17339434
Br Med J. 1957 Apr 6;1(5022):779-86
13404306
Am J Reprod Immunol. 2005 Dec;54(6):369-77
16305662
J Immunol. 2006 Jul 15;177(2):896-904
16818744
Immunity. 2007 Oct;27(4):635-46
17919943
J Leukoc Biol. 2004 May;75(5):785-91
14694186
Nat Immunol. 2006 Jun;7(6):551-3
16715063
Pancreas. 2006 Nov;33(4):386-90
17079944
J Transl Med. 2008 Mar 11;6:12
18334033
Oncol Res. 1994;6(4-5):219-28
7841545
Blood. 2007 Oct 1;110(7):2501-10
17575071
J Immunol. 2004 May 15;172(10):6003-10
15128783
Cancer Res. 2003 Sep 1;63(17):5218-23
14500348
J Exp Med. 2002 Mar 4;195(5):603-16
11877483
Cancer Res. 2001 May 1;61(9):3689-97
11325840
Cancer Res. 2007 Sep 15;67(18):8900-5
17875732
Annu Rev Immunol. 2007;25:243-65
17129181
Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):931-6
11792864
Immunity. 2004 Oct;21(4):503-13
15485628
J Immunol. 2002 May 1;168(9):4272-6
11970966
Eur J Haematol. 1993 May;50(5):292-6
7686506
Cancer Res. 2005 Sep 15;65(18):8059-64
16166275
J Clin Invest. 2005 Dec;115(12):3623-33
16308572
PLoS One. 2006 Dec 27;1:e129
17205133
Nat Clin Pract Oncol. 2006 Dec;3(12):668-81
17139318
Immunity. 2003 Aug;19(2):165-8
12932350
J Exp Med. 2001 Sep 17;194(6):823-32
11560997
Immunol Rev. 2007 Dec;220:47-59
17979839
Nat Immunol. 2003 Apr;4(4):330-6
12612578
Cancer Clin Trials. 1979 Winter;2(4):345-50
394870
Nat Rev Cancer. 2007 Nov;7(11):880-7
17957190
Eur J Immunol. 2007 Jan;37(1):129-38
17154262
J Immunother. 2007 Feb-Mar;30(2):240-50
17471171
Cancer. 2006 Dec 15;107(12):2866-72
17099880
J Urol. 2006 Jul;176(1):91-5
16753376
Hematol Cell Ther. 1996 Dec;38 Suppl 2:S75-81
9137960
J Immunother. 2005 Nov-Dec;28(6):582-92
16224276
Cancer Immunol Immunother. 2008 May;57(5):623-34
17899077
J Clin Oncol. 2004 Feb 1;22(3):403-15
14691123
Cancer Res. 2002 Jul 15;62(14):3914-9
12124318
Hum Gene Ther. 2004 Mar;15(3):313-37
15018740
Eur J Immunol. 2007 Nov;37(11):3021-9
17874423
Transpl Immunol. 2008 Jan;18(3):208-19
18047928
Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18538-43
16344461
J Exp Med. 1975 Mar 1;141(3):697-702
1117258
J Immunother. 2006 Mar-Apr;29(2):208-14
16531821
Mol Ther. 2005 Nov;12(5):922-32
16257383
Int J Cancer. 2007 Oct 15;121(8):1749-55
17582606
J Immunol. 2004 May 15;172(10):5986-93
15128781
Cancer Res. 1999 Jul 1;59(13):3128-33
10397255
Gastroenterology. 2007 Jun;132(7):2328-39
17570208
J Immunol. 2004 Jun 1;172(11):6735-43
15153490
J Immunol. 2001 Jun 15;166(12):7282-9
11390478
Int J Cancer. 2007 Dec 1;121(11):2473-83
17691114
Adv Cancer Res. 1979;29:45-125
382778
Nature. 1974 Jun 14;249(458):654-6
4275846
Am J Surg. 1997 Sep;174(3):258-65
9324133
Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15478-83
17875988
J Thorac Oncol. 2008 Apr;3(4):447-50
18379369
J Exp Med. 2002 Jul 15;196(2):237-46
12119348
Cancer Res. 2006 Apr 15;66(8):4488-95
16618776
J Immunol. 2008 Mar 15;180(6):3782-8
18322184
Clin Cancer Res. 2001 May;7(5):1287-92
11350896
J Immunol. 2001 Dec 1;167(11):6669-77
11714839
J Exp Med. 2005 Mar 7;201(5):737-46
15753207
J Transl Med. 2007 Sep 14;5:43
17868452
Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4345-54
17671115
Immunol Rev. 2001 Aug;182:18-32
11722621
J Immunother. 2004 Sep-Oct;27(5):339-46
15314542
Immunity. 2006 Sep;25(3):455-71
16973386
Cancer Res. 1986 May;46(5):2572-7
3697996
J Immunol. 2000 Oct 15;165(8):4246-53
11035058
J Immunol. 2007 Oct 1;179(7):4919-28
17878392
Int Immunol. 2007 Apr;19(4):345-54
17329235
Nature. 1976 Jul 1;262(5563):77-8
1084484
J Immunol. 2005 Aug 1;175(3):1483-90
16034085
J Exp Med. 2004 Jul 19;200(2):149-57
15249593
Br J Cancer. 2007 Feb 26;96(4):617-22
17262084
Cancer Immunol Immunother. 2007 May;56(5):641-8
16960692
J Immunol. 2007 Aug 15;179(4):2105-14
17675469
Cancer. 1980 Feb 15;45(4):742-9
6986970
Eur J Immunol. 2004 Feb;34(2):336-44
14768038
J Exp Med. 2003 Dec 15;198(12):1875-86
14676299
Immunity. 2004 Aug;21(2):267-77
15308106
J Immunol. 1995 Aug 1;155(3):1151-64
7636184
Curr Opin Immunol. 2007 Apr;19(2):217-23
17306521
Immunity. 2006 Sep;25(3):441-54
16973387
Nat Rev Immunol. 2003 Mar;3(3):253-7
12658273
J Immunol. 2007 Feb 15;178(4):2155-62
17277120
Eur J Immunol. 2004 Dec;34(12):3485-96
15484187
J Immunother. 2007 Apr;30(3):294-302
17414320
J Exp Med. 2006 Mar 20;203(3):505-11
16533880
Nat Immunol. 2005 Nov;6(11):1142-51
16227984
Cancer Res. 2005 Jun 15;65(12):5211-20
15958566
J Exp Med. 2008 Apr 14;205(4):825-39
18362171
PLoS One. 2008 Apr 23;3(4):e1983
18431473
Blood. 2007 Jan 15;109(2):632-42
16985181
J Immunol. 2000 Jan 1;164(1):107-12
10605000
Blood. 2005 Apr 1;105(7):2845-51
15591118
Science. 2007 Nov 16;318(5853):1108-13
17932254
J Exp Med. 2004 Sep 20;200(6):771-82
15381730
Immunity. 2006 Jul;25(1):129-41
16860762