title: Chemoimmunotherapy: reengineering tumor immunity.
abstract: Cancer chemotherapy drugs have long been considered immune suppressive. However, more recent data indicate that some cytotoxic drugs effectively treat cancer in part by facilitating an immune response to the tumor when given at the standard dose and schedule. These drugs induce a form of tumor cell death that is immunologically active, thereby inducing an adaptive immune response specific for the tumor. In addition, cancer chemotherapy drugs can promote tumor immunity through ancillary and largely unappreciated immunologic effects on both the malignant and normal host cells present within the tumor microenvironment. These more subtle immunomodulatory effects are dependent on the drug itself, its dose, and its schedule in relation to an immune-based intervention. The recent approvals of two new immune-based therapies for prostate cancer and melanoma herald a new era in cancer treatment and have led to heightened interest in immunotherapy as a valid approach to cancer treatment. A detailed understanding of the cellular and molecular basis of interactions between chemotherapy drugs and the immune system is essential for devising the optimal strategy for integrating new immune-based therapies into the standard of care for various cancers, resulting in the greatest long-term clinical benefit for cancer patients.
authors: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231-1000, USA.
authors: Gang
authors: G
authors: Chen
authors: Leisha A
authors: LA
authors: Emens
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002986:Clinical Trials as Topic; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy*; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents
references: Blood. 2005 Sep 15;106(6):2018-25
references: 15914560
references: N Engl J Med. 2012 Jun 28;366(26):2455-65
references: 22658128
references: J Immunol. 2001 Jun 1;166(11):6491-9
references: 11359799
references: Cancer Res. 2011 May 15;71(10):3528-39
references: 21444678
references: Cell Immunol. 2010;261(2):134-43
references: 20036354
references: Leukemia. 2004 Jul;18(7):1223-30
references: 15152266
references: Breast Cancer Res. 2004;6(4):R275-83
references: 15217493
references: Clin Cancer Res. 2008 Mar 1;14(5):1455-63
references: 18316569
references: J Immunol. 2004 Apr 1;172(7):4599-608
references: 15034078
references: J Immunol. 2009 Jul 1;183(1):137-44
references: 19535620
references: Nat Rev Immunol. 2008 Jan;8(1):59-73
references: 18097448
references: Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):878-87
references: 16467102
references: J Immunol. 1996 Jun 15;156(12):4609-16
references: 8648103
references: Blood. 2000 May 15;95(10):3011-9
references: 10807763
references: Cancer Immunol Immunother. 2011 Sep;60(9):1227-42
references: 21544650
references: Science. 2002 Oct 25;298(5594):850-4
references: 12242449
references: Oncologist. 2011;16(8):1092-100
references: 21572124
references: Nat Med. 2012 Aug;18(8):1254-61
references: 22842478
references: Clin Cancer Res. 2010 Sep 15;16(18):4583-94
references: 20702612
references: J Clin Oncol. 2012 Jun 10;30(17):2046-54
references: 22547592
references: Science. 2011 Dec 16;334(6062):1573-7
references: 22174255
references: J Clin Oncol. 2009 Dec 10;27(35):5911-8
references: 19805669
references: Clin Cancer Res. 2008 Aug 1;14(15):4843-9
references: 18676757
references: Clin Cancer Res. 2005 Aug 15;11(16):5993-6001
references: 16115944
references: Clin Cancer Res. 2008 May 15;14(10):3185-92
references: 18483387
references: N Engl J Med. 2010 Aug 19;363(8):711-23
references: 20525992
references: Clin Cancer Res. 2006 Feb 15;12(4):1260-9
references: 16489082
references: Blood. 2000 Mar 15;95(6):2024-30
references: 10706870
references: J Transl Med. 2009 Jul 10;7:58
references: 19591684
references: Blood. 2010 Jun 3;115(22):4384-92
references: 20154220
references: Blood. 2010 May 13;115(19):3869-78
references: 20071660
references: Cancer Res. 2001 May 1;61(9):3689-97
references: 11325840
references: Curr Opin Investig Drugs. 2009 Dec;10(12):1315-24
references: 19943203
references: Clin Cancer Res. 2010 Jun 15;16(12):3100-4
references: 20421432
references: Cancer Immunol Immunother. 2009 Oct;58(10):1627-34
references: 19221744
references: Nat Med. 2009 Oct;15(10):1170-8
references: 19767732
references: Cancer Res. 2008 Jul 15;68(14):5955-64
references: 18632651
references: N Engl J Med. 2012 Jun 28;366(26):2443-54
references: 22658127
references: Int J Cancer. 2006 Jun 1;118(11):2888-98
references: 16380982
references: Nat Rev Immunol. 2009 Mar;9(3):162-74
references: 19197294
references: Cancer Immunol Immunother. 2010 Jan;59(1):137-48
references: 19590872
references: Eur J Immunol. 2001 Aug;31(8):2448-57
references: 11500829
references: Int Immunopharmacol. 2009 Jul;9(7-8):900-9
references: 19336265
references: PLoS One. 2009 Sep 10;4(9):e6982
references: 19746156
references: Clin Cancer Res. 2008 Jul 1;14(13):4192-9
references: 18593999
references: J Immunol. 2000 Jun 15;164(12):6230-6
references: 10843675
references: Blood. 2005 Apr 1;105(7):2862-8
references: 15591121
references: Oncology (Williston Park). 2003 Sep;17(9):1200-11; discussion 1214, 1217-8
references: 14569849
references: J Immunother. 2006 Jul-Aug;29(4):367-80
references: 16799332
references: Clin Cancer Res. 2001 May;7(5):1181-91
references: 11350882
references: J Immunol. 2011 Dec 1;187(11):6130-42
references: 22048768
references: Nat Rev Immunol. 2009 May;9(5):353-63
references: 19365408
references: Oncoimmunology. 2012 May 1;1(3):271-278
references: 22737602
references: J Exp Med. 2000 Aug 21;192(4):549-56
references: 10952724
references: Cancer Res. 2003 Dec 1;63(23):8408-13
references: 14679003
references: Cancer Res. 2011 Feb 1;71(3):661-5
references: 21148486
references: Ann Surg. 2011 Feb;253(2):328-35
references: 21217520
references: Br J Cancer. 2009 Jun 2;100(11):1697-703
references: 19384299
references: Cancer Immunol Immunother. 2009 Apr;58(4):589-601
references: 18791715
references: J Exp Med. 2005 May 16;201(10):1591-602
references: 15883172
references: Blood. 2011 Jan 13;117(2):608-17
references: 20935254
references: Cancer Immunol Immunother. 2009 Jan;58(1):49-59
references: 18446337
references: Oncogene. 2010 Jan 28;29(4):482-91
references: 19881547
references: Int J Cancer. 2003 Apr 20;104(4):437-45
references: 12584740
references: J Transl Med. 2010 Jul 23;8:71
references: 20653948
references: Blood. 2009 Aug 27;114(9):1736-45
references: 19556425
references: Clin Cancer Res. 2007 Jun 1;13(11):3333-8
references: 17545540
references: Blood. 2010 Mar 25;115(12):2397-406
references: 20118405
references: Nat Med. 2005 Nov;11(11):1230-7
references: 16227990
references: Clin Cancer Res. 2001 Oct;7(10):3025-30
references: 11595690
references: Clin Cancer Res. 2011 Jul 1;17(13):4568-80
references: 21586625
references: Curr Opin Mol Ther. 2001 Feb;3(1):77-84
references: 11249735
references: BMC Immunol. 2010 Mar 19;11:14
references: 20302610
references: Nat Med. 2007 Sep;13(9):1050-9
references: 17704786
references: Ann Oncol. 2013 Jan;24(1):75-83
references: 22858559
references: Cancer Immunol Immunother. 2012 May;61(5):629-41
references: 22021066
references: Cancer Res. 2010 Apr 15;70(8):3052-61
references: 20388795
references: Int J Cancer. 2009 Jan 1;124(1):130-9
references: 18839429
references: J Immunol. 2010 Feb 15;184(4):1737-47
references: 20083664
references: J Clin Invest. 2010 Apr;120(4):1111-24
references: 20234093
references: J Exp Med. 2000 Aug 21;192(4):557-64
references: 10952725
references: Cell Oncol (Dordr). 2011 Apr;34(2):97-106
references: 21290210
references: Clin Cancer Res. 2011 Nov 1;17(21):6847-57
references: 21918169
references: Cell Immunol. 2010;263(1):79-87
references: 20346445
references: Cancer Res. 2001 Jan 1;61(1):162-71
references: 11196155
references: Target Oncol. 2012 Mar;7(1):55-68
references: 22383042
references: Nat Rev Immunol. 2010 Apr;10(4):248-56
references: 20336152
references: Blood. 2003 Feb 15;101(4):1645-52
references: 12406877
references: J Immunol. 2009 Feb 15;182(4):2030-40
references: 19201856
references: Nature. 2011 Dec 21;480(7378):480-9
references: 22193102
references: J Exp Med. 2005 Dec 19;202(12):1691-701
references: 16365148
references: Cancer Immunol Immunother. 2006 Oct;55(10):1285-93
references: 16408214
references: N Engl J Med. 2011 Jun 30;364(26):2517-26
references: 21639810
references: Nat Rev Immunol. 2006 Apr;6(4):295-307
references: 16557261
references: Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15825-30
references: 19717467
references: J Immunol. 2006 Mar 1;176(5):2722-9
references: 16493027
references: Cancer Immunol Immunother. 2007 May;56(5):641-8
references: 16960692
references: Br J Haematol. 2002 Aug;118(2):638-45
references: 12139759
references: Eur J Immunol. 2004 Feb;34(2):336-44
references: 14768038
references: N Engl J Med. 2010 Jul 29;363(5):411-22
references: 20818862
references: J Biol Chem. 2000 Jan 28;275(4):2251-4
references: 10644670
references: Clin Immunol. 2008 Nov;129(2):219-29
references: 18771959
references: J Clin Oncol. 2008 Nov 10;26(32):5233-9
references: 18809613
references: Cancer Res. 2010 Sep 15;70(18):7084-92
references: 20823160
references: Cancer Res. 2009 May 15;69(10):4309-18
references: 19435909
references: Mol Ther. 2010 Jun;18(6):1233-43
references: 20372107
references: J Clin Oncol. 2005 Dec 10;23(35):8950-8
references: 16061910
references: Breast Cancer Res. 2010;12(4):R48
references: 20626886