1. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet 2018;391:1301-1314.
2. Llovet JM, Zucman-Rossi J, Pikarsky E, Sangro B, Schwartz M, Sherman M, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2016;2:16018.
3. Cheng AL, Kang YK, Lin DY, Park JW, Kudo M, Qin S, et al. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol 2013;31:4067-4075.
4. Johnson PJ, Qin S, Park JW, Poon R, Raoul JL, Philip PA, et al. Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL study. J Clin Oncol 2013;31:3517-3524.
5. Zhu AX, Rosmorduc O, Evans T, Ross PJ, Santoro A, Carrilho FJ, et al. SEARCH: a phase III, randomized, double-blind, placebocontrolled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2014;33:559-566.
6. Abou-Alfa GK, Capanu M, O’Reilly EM, Ma J, Chou JF, Gansukh B, et al. A phase II study of cixutumumab (IMC-A12, NSC742460) in advanced hepatocellular carcinoma. J Hepatol 2014;60:319-324.
7. Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 noninferiority trial. Lancet 2018;391:1163-1173.
8. Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, doubleblind, placebo-controlled, phase 3 trial. Lancet 2017;389:56-66.
11. Greten TF, Manns MP, Korangy F. Immunotherapy of hepatocellular carcinoma. J Hepatol 2006;45:868-878.
12. Greten TF, Manns MP, Korangy F. Immunotherapy of HCC. Rev Recent Clin Trials 2008;3:31-39.
13. El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 2017;389:2492-2502.
15. Knolle P, Schlaak J, Uhrig A, Kempf P, Meyer zum Büschenfelde KH, Gerken G. Human Kupffer cells secrete IL-10 in response to lipopolysaccharide (LPS) challenge. J Hepatol 1995;22:226-229.
18. Schmidt N, Thimme R. Role of immunity in pathogenesis and treatment of hepatocellular carcinoma. Dig Dis 2016;34:429-437.
19. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-674.
22. Lee JH, Lee JH, Lim YS, Yeon JE, Song TJ, Yu SJ, et al. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma. Gastroenterology 2015;148:1383-1391.e1386.
25. Badalamenti G, Fanale D, Incorvaia L, Barraco N, Listì A, Maragliano R, et al. Role of tumor-infiltrating lymphocytes in patients with solid tumors: Can a drop dig a stone? Cell Immunol 2018 Feb 1;doi: 10.1016/j.cellimm.2018.01.013. [Epub ahead of print].
31. Sangro B, Gomez-Martin C, de la Mata M, Iñarrairaegui M, Garralda E, Barrera P, et al. A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C. J Hepatol 2013;59:81-88.
32. Duffy AG, Ulahannan SV, Makorova-Rusher O, Rahma O, Wedemeyer H, Pratt D, et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J Hepatol 2017;66:545-551.
33. El-Khoueiry AB, Melero I, Crocenzi TS, Welling TH, Yau TC, Yeo W, et al. Phase I/II safety and antitumor activity of nivolumab in patients with advanced hepatocellular carcinoma (HCC): CA209-040. ASCO 2015;33:18.
34. Zhong F, Cheng X, Sun S, Zhou J. Transcriptional activation of PD-L1 by Sox2 contributes to the proliferation of hepatocellular carcinoma cells. Oncol Rep 2017;37:3061-3067.
35. Gao Q, Wang XY, Qiu SJ, Yamato I, Sho M, Nakajima Y, et al. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res 2009;15:971-979.
36. Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015;372:320-330.
38. Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a nonrandomised, open-label phase 2 trial. Lancet Oncol 2018;19:940-952.
41. Zerbini A, Pilli M, Penna A, Pelosi G, Schianchi C, Molinari A, et al. Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses. Cancer res 2006;66:1139-1146.
42. Mizukoshi E, Yamashita T, Arai K, Sunagozaka H, Ueda T, Arihara F, et al. Enhancement of tumor‐associated antigen‐specific T cell responses by radiofrequency ablation of hepatocellular carcinoma. Hepatology 2013;57:1448-1457.
44. Butterfield LH, Ribas A, Meng WS, Dissette VB, Amarnani S, Vu HT, et al. T-cell responses to HLA-A*0201 immunodominant peptides derived from alpha-fetoprotein in patients with hepatocellular cancer. Clin Cancer Res 2003;9(16 Pt 1):5902-5908.
46. Ormandy LA, Farber A, Cantz T, Petrykowska S, Wedemeyer H, Horning M, et al. Direct ex vivo analysis of dendritic cells in patients with hepatocellular carcinoma. World J Gastroenterol WJG 2006;12:3275-3282.
47. Shang N, Figini M, Shangguan J, Wang B, Sun C, Pan L, et al. Dendritic cells based immunotherapy. Am J Cancer Res 2017;7:2091-2102.
50. Bourke M, Salwa S, Harrington K, Kucharczyk M, Forde P, de Kruijf M, et al. The emerging role of viruses in the treatment of solid tumours. Cancer Treat Rev 2011;37:618-632.
51. Stanford MM, Bell JC, Vähä-Koskela MJ. Novel oncolytic viruses: riding high on the next wave? Cytokine Growth Factor Rev 2010;21:177-183.
54. Breitbach CJ, Arulanandam R, De Silva N, Thorne SH, Patt R, Daneshmand M, et al. Oncolytic vaccinia virus disrupts tumorassociated vasculature in humans. Cancer Res 2013;73:1265-1275.
56. Weber JS, Hodi FS, Wolchok JD, Topalian SL, Schadendorf D, Larkin J, et al. Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma. J Clin Oncol 2017;35:785-792.
57. Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med 2018;378:158-168.
58. Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the immune-related adverse effects of immune checkpoint inhibitors: a review. JAMA Oncol 2016;2:1346-1353.
59. Menzies AM, Johnson DB, Ramanujam S, Atkinson VG, Wong ANM, Park JJ, et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol 2017;28:368-376.