title: Hepatocellular carcinoma from an immunologic perspective.
abstract: Hepatocellular carcinoma is the third most common cancer worldwide. It is an inflammation-associated cancer. Multiple investigators have demonstrated that analysis of the tumor microenvironment may be used to predict patient outcome, indicating the importance of local immune responses in this disease. In contrast with other types of cancer, in which surgery, radiation, and systemic cytotoxic chemotherapies dominate the treatment options, in hepatocellular carcinoma locoregional treatments are widely applied. Such treatments induce rapid tumor cell death and antitumor immune responses, which may favor or impair the patients' outcome. Recent immunotherapeutic studies demonstrating promising results include trials evaluating intratumoral injection of an oncolytic virus expressing granulocyte macrophage colony-stimulating factor, glypican-3 targeting treatments, and anti-CTLA4 treatment. Although some of these novel approaches may provide benefit as single agents, there is a clear opportunity in hepatocellular carcinoma to evaluate these in combination with the standard modalities to more effectively harness the immune response.
authors.affiliation: Authors' Affiliation: GI-Malignancy Section, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Tim F
authors.initials: TF
authors.lastname: Greten
authors.forename: Austin G
authors.initials: AG
authors.lastname: Duffy
authors.forename: Firouzeh
authors.initials: F
authors.lastname: Korangy
mesh_terms: D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate; D007167:Immunotherapy; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D050504:Oncolytic Viruses; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
references.citation: N Engl J Med. 2008 Jul 24;359(4):378-90
references.pmid: 18650514
references.citation: Ultrasound Med Biol. 2004 Sep;30(9):1217-22
references.pmid: 15550325
references.citation: Rev Recent Clin Trials. 2008 Jan;3(1):31-9
references.pmid: 18474013
references.citation: J Gastroenterol. 2010 Apr;45(4):451-8
references.pmid: 19936602
references.citation: J Hepatol. 2012 Nov;57(5):1013-20
references.pmid: 22732513
references.citation: World J Gastroenterol. 2006 Jun 21;12(23):3716-21
references.pmid: 16773688
references.citation: J Hepatol. 2006 Dec;45(6):868-78
references.pmid: 17046096
references.citation: Gastroenterology. 2003 Jul;125(1):89-97
references.pmid: 12851874
references.citation: FEBS J. 2013 May;280(10):2471-6
references.pmid: 23305321
references.citation: N Engl J Med. 2010 Aug 19;363(8):711-23
references.pmid: 20525992
references.citation: Nat Rev Cancer. 2007 Feb;7(2):95-106
references.pmid: 17251916
references.citation: Nat Med. 2013 Mar;19(3):329-36
references.pmid: 23396206
references.citation: Mol Ther. 2008 Sep;16(9):1637-42
references.pmid: 18628758
references.citation: Cancer Immunol Immunother. 2013 Apr;62(4):737-46
references.pmid: 23223899
references.citation: Cancer Res. 2005 Jul 15;65(14):6245-54
references.pmid: 16024626
references.citation: J Immunol. 2007 Feb 1;178(3):1914-22
references.pmid: 17237442
references.citation: J Clin Oncol. 2007 Jun 20;25(18):2586-93
references.pmid: 17577038
references.citation: Br J Cancer. 2006 Oct 9;95(7):896-905
references.pmid: 16953240
references.citation: Gastroenterology. 2010 May;138(5):1931-42
references.pmid: 20060829
references.citation: J Hepatol. 2013 Nov;59(5):1007-13
references.pmid: 23796475
references.citation: Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):E1083-91
references.pmid: 23471984
references.citation: J Hepatol. 2012 Apr;56(4):908-43
references.pmid: 22424438
references.citation: J Hepatol. 2012 Mar;56(3):686-95
references.pmid: 21971559
references.citation: Lancet Oncol. 2008 Jun;9(6):533-42
references.pmid: 18495536
references.citation: Hum Vaccin Immunother. 2013 Jun;9(6):1228-33
references.pmid: 23466818
references.citation: Hepatology. 2011 Apr;53(4):1206-16
references.pmid: 21480325
references.citation: Cancer Immunol Immunother. 2013 Aug;62(8):1421-30
references.pmid: 23764929
references.citation: Gastroenterology. 2007 Jun;132(7):2328-39
references.pmid: 17570208
references.citation: Clin Cancer Res. 2009 Dec 1;15(23):7412-20
references.pmid: 19934295
references.citation: N Engl J Med. 2012 Mar 8;366(10):925-31
references.pmid: 22397654
references.citation: Nat Rev Drug Discov. 2012 Feb 03;11(3):215-33
references.pmid: 22301798
references.citation: Cell. 2010 Jan 22;140(2):197-208
references.pmid: 20141834
references.citation: Clin Cancer Res. 2004 Jul 1;10(13):4332-41
references.pmid: 15240519
references.citation: Clin Dev Immunol. 2012;2012:607851
references.pmid: 22666283
references.citation: N Engl J Med. 2008 Nov 6;359(19):1995-2004
references.pmid: 18923165
references.citation: Clin Cancer Res. 2012 Jul 1;18(13):3686-96
references.pmid: 22577059
references.citation: Cancer Gene Ther. 1999 Sep-Oct;6(5):409-22
references.pmid: 10505851
references.citation: Cancer Cell. 2006 Aug;10(2):99-111
references.pmid: 16904609
references.citation: Nat Rev Cancer. 2009 Jan;9(1):64-71
references.pmid: 19104515
references.citation: Hepatology. 2009 Sep;50(3):799-807
references.pmid: 19551844
references.citation: J Hepatol. 2010 Oct;53(4):775-6
references.pmid: 20619917
references.citation: N Engl J Med. 1997 Jun 26;336(26):1855-9
references.pmid: 9197213
references.citation: J Immunother. 2008 Apr;31(3):271-82
references.pmid: 18317360
references.citation: Cancer Res. 2006 Jan 15;66(2):1139-46
references.pmid: 16424051
references.citation: Semin Oncol. 2012 Aug;39(4):473-85
references.pmid: 22846864
references.citation: PLoS One. 2011;6(9):e23621
references.pmid: 21912640
references.citation: Hepatology. 2010 May;51(5):1820-32
references.pmid: 20432259
references.citation: Int J Oncol. 2012 Jan;40(1):63-70
references.pmid: 21922136
references.citation: Hepatology. 2013 Apr;57(4):1448-57
references.pmid: 23174905
references.citation: Hepatology. 2009 Feb;49(2):658-64
references.pmid: 19177576
references.citation: J Hepatol. 2013 Jul;59(1):81-8
references.pmid: 23466307
references.citation: Am J Surg. 2012 Jan;203(1):101-6
references.pmid: 21429472
references.citation: CA Cancer J Clin. 2013 Jan;63(1):11-30
references.pmid: 23335087