title: Subverting the B7-H1/PD-1 pathway in advanced melanoma and kidney cancer.
abstract: Ligands for inhibitory immune receptors on T cells may be constitutively expressed on tumor cells or host cells in tumor microenvironment as a consequence of adaptive immunity. Programmed death 1 (PD-1) is 1 such receptor on T cells, which functions as a negative regulator of T cell activity. Tumors that up-regulate programmed death ligand 1 (PD-L1) (B7-H1) may abrogate the host's effector T cell antitumor response. Higher tumoral PD-L1 expression has been linked with inferior clinical outcomes. Multiple cancers including renal cell cancers (RCCs) and melanomas have relatively high levels of PD-L1 on the cell surface. Early evaluations of antibodies that block the interaction of PD-1 and PD-L1 have shown efficacy and a favorable tolerability profile with notable inflammatory toxicities that are generally manageable. Upward of 30% of RCC patients and 50% of melanoma patients achieve objective responses. Durable responses can occur, even in some patients who have discontinued treatment. The developing investigation of PD-1/PD-L1 pathway-blocking agents in RCC and melanoma will likely alter our approaches to the treatment of these 2 deadly diseases.
authors.affiliation: From the *Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA †Department of Oncology and the Brady Urological Institute, Johns Hopkins University, Baltimore, MD; and ‡Melanoma Disease Center and Center for Immuno-oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Harshman
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.forename: Charles
authors.initials: C
authors.lastname: Drake
authors.forename: F
authors.initials: F
authors.lastname: Stephen Hodi
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000276:immunology*; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D060890:B7-H1 Antigen; D061026:Programmed Cell Death 1 Receptor
references.citation: PLoS One. 2013 Nov 13;8(11):e78980
references.pmid: 24232460
references.citation: Clin Cancer Res. 2007 Mar 15;13(6):1757-61
references.pmid: 17363529
references.citation: Clin Cancer Res. 2007 Mar 15;13(6):1749-56
references.pmid: 17363528
references.citation: J Clin Oncol. 2014 Apr 1;32(10):1020-30
references.pmid: 24590637
references.citation: N Engl J Med. 2011 Jun 30;364(26):2507-16
references.pmid: 21639808
references.citation: J Immunol. 2004 May 15;172(10):6074-9
references.pmid: 15128791
references.citation: Cancer. 2010 Sep 15;116(18):4256-65
references.pmid: 20549832
references.citation: Clin Cancer Res. 2015 Oct 1;21(19):4286-93
references.pmid: 25977344
references.citation: Lancet. 2011 Dec 3;378(9807):1931-9
references.pmid: 22056247
references.citation: Lancet Oncol. 2013 May;14(6):552-62
references.pmid: 23598172
references.citation: N Engl J Med. 2012 Feb 23;366(8):707-14
references.pmid: 22356324
references.citation: N Engl J Med. 2013 Aug 22;369(8):722-31
references.pmid: 23964934
references.citation: Clin Cancer Res. 2011 Aug 15;17(16):5233-8
references.pmid: 21700764
references.citation: Eur J Cancer. 2014 Feb;50(3):553-62
references.pmid: 24215846
references.citation: J Clin Oncol. 2010 Feb 20;28(6):1061-8
references.pmid: 20100962
references.citation: N Engl J Med. 2012 Jun 28;366(26):2455-65
references.pmid: 22658128
references.citation: N Engl J Med. 2012 Jul 12;367(2):107-14
references.pmid: 22663011
references.citation: N Engl J Med. 2010 Aug 19;363(8):711-23
references.pmid: 20525992
references.citation: Cancer Immunol Res. 2013 Jul;1(1):32-42
references.pmid: 24777248
references.citation: Neuroreport. 2009 Dec 9;20(18):1597-602
references.pmid: 19875977
references.citation: J Clin Oncol. 2010 May 1;28(13):2144-50
references.pmid: 20368553
references.citation: J Clin Oncol. 2013 Dec 1;31(34):4311-8
references.pmid: 24145345
references.citation: J Clin Oncol. 2011 May 1;29(13):1750-6
references.pmid: 21444868
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17174-9
references.pmid: 15569934
references.citation: Clin Cancer Res. 2013 Feb 1;19(3):598-609
references.pmid: 23095323
references.citation: J Clin Oncol. 1995 Mar;13(3):688-96
references.pmid: 7884429
references.citation: N Engl J Med. 2012 Mar 8;366(10):883-892
references.pmid: 22397650
references.citation: N Engl J Med. 2012 Jun 28;366(26):2443-54
references.pmid: 22658127
references.citation: Am J Respir Crit Care Med. 2010 Aug 1;182(3):396-403
references.pmid: 20194812
references.citation: J Clin Oncol. 2013 Oct 20;31(30):3791-9
references.pmid: 24019545
references.citation: Clin Cancer Res. 2007 Jan 15;13(2 Pt 2):709s-715s
references.pmid: 17255298
references.citation: Clin Cancer Res. 2009 Dec 1;15(23):7412-20
references.pmid: 19934295
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10691-6
references.pmid: 15249675
references.citation: Cancer. 2008 Jul 15;113(2):293-301
references.pmid: 18457330
references.citation: Clin Cancer Res. 2008 May 15;14(10):3044-51
references.pmid: 18483370
references.citation: Nat Med. 2002 Aug;8(8):793-800
references.pmid: 12091876
references.citation: J Cancer. 2014 Jan 24;5(3):166-72
references.pmid: 24563671
references.citation: N Engl J Med. 2013 Jul 11;369(2):122-33
references.pmid: 23724867
references.citation: Cancer Res. 2012 Feb 15;72(4):917-27
references.pmid: 22186141
references.citation: Cancer Immunol Res. 2014 Apr;2(4):320-31
references.pmid: 24764579
references.citation: Nat Immunol. 2009 Nov;10(11):1185-92
references.pmid: 19783989
references.citation: Cancer. 2010 Apr 1;116(7):1757-66
references.pmid: 20143437
references.citation: PLoS One. 2011 Mar 07;6(3):e17621
references.pmid: 21408177
references.citation: Lancet. 2008 Aug 9;372(9637):449-56
references.pmid: 18653228
references.citation: J Clin Oncol. 2010 May 1;28(13):2137-43
references.pmid: 20368558
references.citation: Cancer Res. 2014 Feb 1;74(3):665-74
references.pmid: 24336068
references.citation: Nat Med. 2007 Jan;13(1):84-8
references.pmid: 17159987
references.citation: N Engl J Med. 2007 May 31;356(22):2271-81
references.pmid: 17538086
references.citation: J Invest Dermatol. 2011 Jun;131(6):1300-7
references.pmid: 21346771
references.citation: Cancer Res. 2006 Apr 1;66(7):3381-5
references.pmid: 16585157
references.citation: Sci Transl Med. 2013 Aug 28;5(200):200ra116
references.pmid: 23986400
references.citation: Cancer. 2009 May 15;115(10 Suppl):2290-7
references.pmid: 19402057
references.citation: Clin Cancer Res. 2012 Dec 15;18(24):6580-7
references.pmid: 23087408
references.citation: N Engl J Med. 2012 Nov;367(18):1694-703
references.pmid: 23020132
references.citation: J Clin Oncol. 2005 Jan 1;23(1):133-41
references.pmid: 15625368
references.citation: J Clin Oncol. 2009 Jul 10;27(20):3312-8
references.pmid: 19451442
references.citation: N Engl J Med. 2013 Jul 11;369(2):134-44
references.pmid: 23724846
references.citation: J Clin Oncol. 2010 Jul 1;28(19):3167-75
references.pmid: 20516446
references.citation: J Clin Oncol. 2009 Aug 1;27(22):3584-90
references.pmid: 19487381
references.citation: Clin Cancer Res. 2013 Mar 1;19(5):1225-31
references.pmid: 23307859