Prospect of the use of checkpoint inhibitors in hepatocellular cancer treatments

Cancer Management and Research

Volumn 9, Issue , 2017, Pages 19-27

  Raufi, Ali ^a   Tirona, Maria Tria ^a  

^a MARSHALL UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cancer immunotherapy; Hepatocellular cancer; Immune checkpoint inhibitors

Indexed keywords

CHECKPOINT KINASE INHIBITOR; DURVALUMAB; NIVOLUMAB; TICILIMUMAB;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANOREXIA; ANTINEOPLASTIC ACTIVITY; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; CANCER IMMUNOTHERAPY; FATIGUE; HUMAN; LIVER CELL CARCINOMA; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; REVIEW; SIDE EFFECT; TRIACYLGLYCEROL LIPASE BLOOD LEVEL; TUMOR ESCAPE;

EID: 85016146204     PISSN: None     EISSN: 11791322     Source Type: Journal    
DOI: 10.2147/CMAR.S111673     Document Type: Review

References (68)

1. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378-390.
2. Blank CU, Haanen JB, Ribas A, Schumacher TN. Cancer immunology. The “cancer immunogram”. Science. 2016;352(6286):658-660.
3. Bowen DG, Zen M, Holz L, Davis T, McCaughan GW, Bertolino P. The site of primary T cell activation is a determinant of the balance between intrahepatic tolerance and immunity. J Clin Invest. 2004;114(5):701-712.
4. Thomson AW, Knolle PA. Antigen-presenting cell function in the tolerogenic liver environment. Nat Rev Immunol. 2010;10(11):753-766.
5. Ormandy LA, Hillemann T, Wedemeyer H, Manns MP, Greten TF, Korangy F. Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma. Cancer Res. 2005;65(6):2457-2464.
6. Chen KJ, Lin SZ, Zhou L, et al. Selective recruitment of regulatory T cell through CCR6-CCL20 in hepatocellular carcinoma fosters tumor progression and predicts poor prognosis. PLoS One. 2011;6(9):e24671.
7. Gao Q, Qiu SJ, Fan J, et al. Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J Clin Oncol. 2007;25(18):2586-2593.
8. Hoechst B, Voigtlaender T, Ormandy L, et al. Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor. Hepatology. 2009;50(3):799-807.
9. Alisa A, Ives A, Pathan AA, et al. Analysis of CD4+T-cell responses to a novel alpha-fetoprotein-derived epitope in hepatocellular carcinoma patients. Clin Cancer Res. 2005;11(18):6686-6694.
10. Zabala M, Lasarte JJ, Perret C, et al. Induction of immunosuppressive molecules and regulatory T cells counteracts the antitumor effect of interleukin-12-based gene therapy in a transgenic mouse model of liver cancer. J Hepatol. 2007;47(6):807-815.
11. Greten TF, Ormandy LA, Fikuart A, et al. Low-dose cyclophosphamide treatment impairs regulatory T cells and unmasks AFP-specific CD4+T-cell responses in patients with advanced HCC. J Immunother. 2010;33(2):211-218.
12. Wildin RS, Ramsdell F, Peake J, et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet. 2001;27(1):18-20.
13. Bennett CL, Christie J, Ramsdell F, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet. 2001;27(1):20-21.
14. Unitt E, Rushbrook SM, Marshall A, et al. Compromised lymphocytes infiltrate hepatocellular carcinoma: the role of T-regulatory cells. Hepatology. 2005;41(4):722-730.
15. Yang XH, Yamagiwa S, Ichida T, et al. Increase of CD4+CD25+regulatory T-cells in the liver of patients with hepatocellular carcinoma. J Hepatol. 2006;45(2):254-262.
16. Shen X, Li N, Li H, Zhang T, Wang F, Li Q. Increased prevalence of regulatory T cells in the tumor microenvironment and its correlation with TNM stage of hepatocellular carcinoma. J Cancer Res Clin Oncol. 2010;136(11):1745-1754.
17. Kobayashi N, Hiraoka N, Yamagami W, et al. FOXP3+regulatory T cells affect the development and progression of hepatocarcinogenesis. Clin Cancer Res. 2007;13(3):902-911.
18. Fu J, Xu D, Liu Z, et al. Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology. 2007;132(7):2328-2339.
19. Zhou J, Ding T, Pan W, Zhu LY, Li L, Zheng L. Increased intratumoral regulatory T cells are related to intratumoral macrophages and poor prognosis in hepatocellular carcinoma patients. Int J Cancer. 2009;125(7):1640-1648.
20. Mueller MM, Fusenig NE. Constitutive expression of G-CSF and GMCSF in human skin carcinoma cells with functional consequence for tumor progression. Int J Cancer. 1999;83(6):780-789.
21. von Boehmer H. Mechanisms of suppression by suppressor T cells. Nat Immunol. 2005;6(4):338-344.
22. Greten TF, Manns MP, Korangy F. Myeloid derived suppressor cells in human diseases. Int Immunopharmacol. 2011;11(7):802-807.
23. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012;12(4):253-268.
24. Hoechst B, Ormandy LA, Ballmaier M, et al. A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4(+)CD25(+)Foxp3(+) T cells. Gastroenterology. 2008;135(1):234-243.
25. Ilkovitch D, Lopez DM. The liver is a site for tumor-induced myeloidderived suppressor cell accumulation and immunosuppression. Cancer Res. 2009;69(13):5514-5521.
26. Arihara F, Mizukoshi E, Kitahara M, et al. Increase in CD14+HLA-DR-/low myeloid-derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis. Cancer Immunol Immunother. 2013;62(8):1421-1430.
27. Cai L, Zhang Z, Zhou L, et al. Functional impairment in circulating and intrahepatic NK cells and relative mechanism in hepatocellular carcinoma patients. Clin Immunol. 2008;129(3):428-437.
28. Han Y, Chen Z, Yang Y, et al. Human CD14+CTLA-4+regulatory dendritic cells suppress T-cell response by cytotoxic T-lymphocyte antigen-4-dependent IL-10 and indoleamine-2,3-dioxygenase production in hepatocellular carcinoma. Hepatology. 2014;59(2):567-579.
29. Shirabe K, Mano Y, Muto J, et al. Role of tumor-associated macrophages in the progression of hepatocellular carcinoma. Surg Today. 2012;42(1):1-7.
30. Kuang DM, Zhao Q, Peng C, et al. Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. J Exp Med. 2009;206(6):1327-1337.
31. Kuang DM, Peng C, Zhao Q, et al. Tumor-activated monocytes promote expansion of IL-17-producing CD8+T cells in hepatocellular carcinoma patients. J Immunol. 2010;185(3):1544-1549.
32. Zhu XD, Zhang JB, Zhuang PY, et al. High expression of macrophage colony-stimulating factor in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma. J Clin Oncol. 2008;26(16):2707-2716.
33. Kuang DM, Zhao Q, Wu Y, et al. Peritumoral neutrophils link inflammatory response to disease progression by fostering angiogenesis in hepatocellular carcinoma. J Hepatol. 2011;54(5):948-955.
34. Mazzocca A, Dituri F, Lupo L, Quaranta M, Antonaci S, Giannelli G. Tumor-secreted lysophostatidic acid accelerates hepatocellular carcinoma progression by promoting differentiation of peritumoral fibroblasts in myofibroblasts. Hepatology. 2011;54(3):920-930.
35. Kojima Y, Acar A, Eaton EN, et al. Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumorpromoting mammary stromal myofibroblasts. Proc Natl Acad Sci U S A. 2010;107(46):20009-20014.
36. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(13):1290.
37. Tatsumi T, Takehara T, Katayama K, et al. Expression of costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on human hepatocellular carcinoma. Hepatology. 1997;25(5):1108-1114.
38. Shi F, Shi M, Zeng Z, et al. PD-1 and PD-L1 upregulation promotes CD8(+) T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients. Int J Cancer. 2011;128(4):887-896.
39. Li FJ, Zhang Y, Jin GX, Yao L, Wu DQ. Expression of LAG-3 is coincident with the impaired effector function of HBV-specific CD8(+) T cell in HCC patients. Immunol Lett. 2013;150(1-2):116-122.
40. Li H, Wu K, Tao K, et al. Tim-3/galectin-9 signaling pathway mediates T-cell dysfunction and predicts poor prognosis in patients with hepatitis B virus-associated hepatocellular carcinoma. Hepatology. 2012;56(4):1342-1351.
41. Stemmer SM, Benjaminov O, Medalia G, et al. CF102 for the treatment of hepatocellular carcinoma: a phase I/II, open-label, dose-escalation study. Oncologist. 2013;18(1):25-26.
42. Pedroza-Gonzalez A, Kwekkeboom J, Sprengers D. T-cell suppression mediated by regulatory T cells infiltrating hepatic tumors can be overcome by GITRL treatment. Oncoimmunology. 2013;2(1):e22450.
43. Pedroza-Gonzalez A, Zhou G, Singh SP, et al. GITR engagement in combination with CTLA-4 blockade completely abrogates immunosuppression mediated by human liver tumor-derived regulatory T cells ex vivo. Oncoimmunology. 2015;4(12):e1051297.
44. Melero I, Hervas-Stubbs S, Glennie M, Pardoll DM, Chen L. Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer. 2007;7(2):95-106.
45. Hoos A, Ibrahim R, Korman A, et al. Development of ipilimumab: contribution to a new paradigm for cancer immunotherapy. Semin Oncol. 2010;37(5):533-546.
46. Weber J. Immune checkpoint proteins: a new therapeutic paradigm for cancer-preclinical background: CTLA-4 and PD-1 blockade. Semin Oncol. 2010;37(5):430-439.
47. Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK, Ledbetter JA. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med. 1991;174(3):561-569.
48. Engelhardt JJ, Sullivan TJ, Allison JP. CTLA-4 overexpression inhibits T cell responses through a CD28-B7-dependent mechanism. J Immunol. 2006;177(2):1052-1061.
49. Waterhouse P, Penninger JM, Timms E, et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science. 1995;270(5238):985-988.
50. Flecken T, Schmidt N, Hild S, et al. Immunodominance and functional alterations of tumor-associated antigen-specific CD8+T-cell responses in hepatocellular carcinoma. Hepatology. 2014;59(4):1415-1426.
51. Gehring AJ, Ho ZZ, Tan AT, et al. Profile of tumor antigen-specific CD8 T cells in patients with hepatitis B virus-related hepatocellular carcinoma. Gastroenterology. 2009;137(2):682-690.
52. Chen Z, Shen S, Peng B, Tao J. Intratumoural GM-CSF microspheres and CTLA-4 blockade enhance the antitumour immunity induced by thermal ablation in a subcutaneous murine hepatoma model. Int J Hyperthermia. 2009;25(5):374-382.
53. Sangro B, Gomez-Martin C, de la Mata M, et al. A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C. J Hepatol. 2013;59(1):81-88.
54. Sprinzl MF, Galle PR. Facing the dawn of immunotherapy for hepatocellular carcinoma. J Hepatol. 2013;59(1):9-10.
55. Jin HT, Anderson AC, Tan WG, et al. Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection. Proc Natl Acad Sci U S A. 2010;107(33):14733-14738.
56. Blackburn SD, Shin H, Haining WN, et al. Coregulation of CD8+T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol. 2009;10(1):29-37.
57. Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992;11(11):3887-3895.
58. Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027-1034.
59. Keir ME, Liang SC, Guleria I, et al. Tissue expression of PD-L1 mediates peripheral T cell tolerance. J Exp Med. 2006;203(4):883-895.
60. Tseng SY, Otsuji M, Gorski K, et al. B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells. J Exp Med. 2001;193(7):839-846.
61. Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793-800.
62. Wang L, Pino-Lagos K, de Vries VC, Guleria I, Sayegh MH, Noelle RJ. Programmed death 1 ligand signaling regulates the generation of adaptive Foxp3+CD4+regulatory T cells. Proc Natl Acad Sci U S A. 2008;105(27):9331-9336.
63. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252-264.
64. Willimsky G, Schmidt K, Loddenkemper C, Gellermann J, Blankenstein T. Virus-induced hepatocellular carcinomas cause antigen-specific local tolerance. J Clin Invest. 2013;123(3):1032-1043.
65. Wherry EJ. T cell exhaustion. Nat Immunol. 2011;12(6):492-499.
66. Hofmeyer KA, Jeon H, Zang X. The PD-1/PD-L1 (B7-H1) pathway in chronic infection-induced cytotoxic T lymphocyte exhaustion. J Biomed Biotechnol. 2011;2011:451694.
67. Gao Q, Wang XY, Qiu SJ, et al. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res. 2009;15(3): 971-979.
68. El-Khoueiry AB, Melero I, Crocenzi TS, et al. Phase I/II safety and antitumor activity of nivolumab in patients with advanced hepatocellular carcinoma (HCC): CA209-040. ASCO Meeting Abstracts. 2015;33(Suppl):LBA101.