title: Acquired resistance to immunotherapy and future challenges.
abstract: Advances in immunotherapy have resulted in remarkable clinical responses in some patients. However, one of the biggest challenges in cancer therapeutics is the development of resistant disease and disease progression on or after therapy. Given that many patients have now received various types of immunotherapy, we asked three scientists to give their views on the current evidence for whether acquired resistance to immunotherapy exists in patients and the future challenges posed by immunotherapy.
authors.affiliation: Center for Cancer Research, National Cancer Institute and Center for Regenerative Medicine, National Institutes of Health, Bldg 10/CRC, Room 3-5762, 9000 Rockville Pike, Bethesda, Maryland 20892, USA.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
authors.affiliation: Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia; and the School of Medicine, University of Queensland, Herston, Brisbane, Queensland 4006, Australia.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, New York, New York 10065, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Snyder
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D060890:B7-H1 Antigen / Q000276:immunology / Q000378:metabolism; D002986:Clinical Trials as Topic; D006801:Humans; D055261:Immunogenetic Phenomena; D007167:Immunotherapy / Q000379:methods*; D000074324:Ipilimumab; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D012641:Selection, Genetic; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D000074324:Ipilimumab
references.citation: Nature. 2007 Dec 6;450(7171):903-7
references.pmid: 18026089
references.citation: Nat Med. 2016 Jan;22(1):26-36
references.pmid: 26735408
references.citation: Nat Immunol. 2002 Nov;3(11):999-1005
references.pmid: 12407407
references.citation: Nature. 2015 Jul 9;523(7559):231-5
references.pmid: 25970248
references.citation: Cancer Discov. 2015 Sep;5(9):915-9
references.pmid: 26272491
references.citation: Nature. 2012 Feb 08;482(7385):405-9
references.pmid: 22318517
references.citation: Science. 2015 Apr 3;348(6230):124-8
references.pmid: 25765070
references.citation: J Exp Med. 2012 Sep 24;209(10):1869-82
references.pmid: 22927549
references.citation: J Exp Med. 2000 Sep 4;192(5):755-60
references.pmid: 10974040
references.citation: Clin Cancer Res. 2009 Dec 1;15(23 ):7412-20
references.pmid: 19934295
references.citation: Proc Natl Acad Sci U S A. 2008 Jun 10;105(23):8061-6
references.pmid: 18523011
references.citation: N Engl J Med. 2015 May 21;372(21):2006-17
references.pmid: 25891304
references.citation: Clin Cancer Res. 2011 Jul 1;17(13):4550-7
references.pmid: 21498393
references.citation: Immunogenetics. 1995;41(4):178-228
references.pmid: 7890324
references.citation: Science. 2011 Mar 25;331(6024):1565-70
references.pmid: 21436444
references.citation: Immunology. 2009 Feb;126(2):186-200
references.pmid: 18557789
references.citation: Nat Rev Immunol. 2012 Mar 22;12(4):269-81
references.pmid: 22437939
references.citation: Nat Rev Cancer. 2012 Mar 22;12(4):252-64
references.pmid: 22437870
references.citation: Cell. 2015 Jan 15;160(1-2):48-61
references.pmid: 25594174
references.citation: J Exp Med. 2002 Jan 21;195(2):161-9
references.pmid: 11805143
references.citation: J Clin Oncol. 2015 Apr 1;33(10):1093-4
references.pmid: 25691668
references.citation: N Engl J Med. 2015 Feb 19;372(8):783
references.pmid: 25693024
references.citation: Blood. 2014 Jul 17;124(3):453-62
references.pmid: 24891321
references.citation: Semin Oncol. 2015 Aug;42(4):523-38
references.pmid: 26320058
references.citation: Science. 2015 Oct 9;350(6257):158-9
references.pmid: 26450194
references.citation: Science. 2015 Apr 3;348(6230):74-80
references.pmid: 25838376
references.citation: Nature. 2012 Feb 08;482(7385):400-4
references.pmid: 22318521
references.citation: Sci Transl Med. 2013 Aug 28;5(200):200ra116
references.pmid: 23986400
references.citation: Clin Cancer Res. 2013 Jul 1;19(13):3462-73
references.pmid: 23674495
references.citation: Clin Cancer Res. 2012 Apr 1;18(7):2039-47
references.pmid: 22271879
references.citation: Oncoimmunology. 2015 Apr 14;4(10):e1029705
references.pmid: 26451299
references.citation: Science. 2015 Apr 3;348(6230):62-8
references.pmid: 25838374
references.citation: Nat Rev Cancer. 2012 Oct;12(10):671-84
references.pmid: 22996603
references.citation: Clin Cancer Res. 2013 Oct 15;19(20):5636-46
references.pmid: 23873688
references.citation: Nature. 2015 Apr 16;520(7547):373-7
references.pmid: 25754329
references.citation: Lancet Oncol. 2015 May;16(5):522-30
references.pmid: 25840693
references.citation: Science. 2015 Oct 9;350(6257):207-11
references.pmid: 26359337
references.citation: Nature. 2014 Nov 27;515(7528):577-81
references.pmid: 25428507
references.citation: Science. 2015 Apr 3;348(6230):69-74
references.pmid: 25838375
references.citation: Cancer Res. 2015 Jun 1;75(11):2139-45
references.pmid: 25977340
references.citation: Clin Cancer Res. 2014 Oct 1;20(19):5064-74
references.pmid: 24714771
references.citation: Nature. 2001 Apr 26;410(6832):1107-11
references.pmid: 11323675
references.citation: N Engl J Med. 2014 Dec 4;371(23 ):2189-99
references.pmid: 25409260
references.citation: N Engl J Med. 2015 Jun 25;372(26):2509-20
references.pmid: 26028255
references.citation: J Natl Cancer Inst. 1996 Jan 17;88(2):100-8
references.pmid: 8537970
references.citation: Yale J Biol Med. 1982 May-Aug;55(3-4):329-33
references.pmid: 6758376
references.citation: Nature. 2012 Oct 18;490(7420):412-6
references.pmid: 23051752