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Immunopathology of Hepatobiliary Tumors and Immunotherapy of Liver Cancers

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Cancer Immunology

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Abstract

Hepatobiliary tumors are a diverse group of tumors that arise from the hepatobiliary tract including the liver, gallbladder, and bile tract. Hepatocellular cancer is the most common type of liver cancer and is usually related to chronic infection with hepatitis virus. Gallbladder cancer is less common in clinical practice, but the prognosis of the patients is very poor. Cholangiocarcinoma, cancer of the bile tract, is complex due to its anatomic segmentation. The mainstay treatment modality for these tumors includes surgery, liver transplantation, interventional therapy, targeted therapy, and chemotherapy. However, for the majority of patients with advanced cancer, the treatment option is limited and the efficacy is not satisfactory. Therefore, the development of novel therapies is highly required. Recently, the role of immunopathology from cancer microenvironment in the process of carcinogenesis and progression has been unveiled. Cytokines and lymphokines such as interleukin-6 and lymphotoxin, together with immune cells such as tumor-associated macrophages, play an important role in this process. Disruption in normal immune regulatory mechanisms provides additional therapeutic targets for cancer. Various immunotherapy strategies are proposed for hepatobiliary cancers including cancer vaccine, adoptive transfer of immune cells, and antibody therapy. This chapter seeks to discuss recent advances in immunopathology of hepatobiliary cancer, with emphasis on immunotherapy in liver cancers at both preclinical and clinical levels.

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References

  1. Kiran RP, Pokala N, Dudrick SJ. Incidence pattern and survival for gallbladder cancer over three decades – an analysis of 10301 patients. Ann Surg Oncol. 2007;14(2):827–32.

    Article  CAS  PubMed  Google Scholar 

  2. Eslick GD. Epidemiology of gallbladder cancer. Gastroenterol Clin N Am. 2010;39(2):307–30.

    Article  Google Scholar 

  3. Wang JH JX (2010) Epidemiology of gallbladder cancer in China. Lit Chin Gen Surg. 6(2).

    Google Scholar 

  4. Patel T. Cholangiocarcinoma. Nat Clin Pract Gastroenterol Hepatol. 2006;3(1):33–42.

    Article  PubMed  Google Scholar 

  5. Lim JH. Cholangiocarcinoma: morphologic classification according to growth pattern and imaging findings. AJR Am J Roentgenol. 2003;181(3):819–27.

    Article  PubMed  Google Scholar 

  6. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    Article  CAS  PubMed  Google Scholar 

  7. Ding ZY, Zou XL, Wei YQ. Cancer microenvironment and cancer vaccine. Cancer Microenviron. 2012;5(3):333–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44.

    Article  CAS  PubMed  Google Scholar 

  9. Nakamoto Y, Guidotti LG, Kuhlen CV, Fowler P, Chisari FV. Immune pathogenesis of hepatocellular carcinoma. J Exp Med. 1998;188(2):341–50.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Haybaeck J, Zeller N, Wolf MJ, Weber A, Wagner U, Kurrer MO, et al. A lymphotoxin-driven pathway to hepatocellular carcinoma. Cancer Cell. 2009;16(4):295–308.

    Article  CAS  PubMed  Google Scholar 

  11. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, et al. A toll-like receptor recognizes bacterial DNA. Nature. 2000;408(6813):740–5.

    Article  CAS  PubMed  Google Scholar 

  12. Tanaka J, Sugimoto K, Shiraki K, Tameda M, Kusagawa S, Nojiri K, et al. Functional cell surface expression of toll-like receptor 9 promotes cell proliferation and survival in human hepatocellular carcinomas. Int J Oncol. 2010;37(4):805–14.

    Article  CAS  PubMed  Google Scholar 

  13. Naugler WE, Karin M. The wolf in sheep’s clothing: the role of interleukin-6 in immunity, inflammation and cancer. Trends Mol Med. 2008;14(3):109–19.

    Article  CAS  PubMed  Google Scholar 

  14. Goydos JS, Brumfield AM, Frezza E, Booth A, Lotze MT, Carty SE. Marked elevation of serum interleukin-6 in patients with cholangiocarcinoma: validation of utility as a clinical marker. Ann Surg. 1998;227(3):398–404.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Giannitrapani L, Cervello M, Soresi M, Notarbartolo M, La Rosa M, Virruso L, et al. Circulating IL-6 and sIL-6R in patients with hepatocellular carcinoma. Ann N Y Acad Sci. 2002;963:46–52.

    Article  CAS  PubMed  Google Scholar 

  16. Giannitrapani L, Soresi M, Giacalone A, Campagna ME, Marasa M, Cervello M, et al. IL-6–174G/C polymorphism and IL-6 serum levels in patients with liver cirrhosis and hepatocellular carcinoma. OMICS. 2011;15(3):183–6.

    Article  CAS  PubMed  Google Scholar 

  17. Wang XH, Liu BR, Qu B, Xing H, Gao SL, Yin JM, et al. Silencing STAT3 may inhibit cell growth through regulating signaling pathway, telomerase, cell cycle, apoptosis and angiogenesis in hepatocellular carcinoma: potential uses for gene therapy. Neoplasma. 2011;58(2):158–71.

    Article  CAS  PubMed  Google Scholar 

  18. Lin L, Amin R, Gallicano GI, Glasgow E, Jogunoori W, Jessup JM, et al. The STAT3 inhibitor NSC 74859 is effective in hepatocellular cancers with disrupted TGF-beta signaling. Oncogene. 2009;28(7):961–72.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Arsura M, Cavin LG. Nuclear factor-kappaB and liver carcinogenesis. Cancer Lett. 2005;229(2):157–69.

    Article  CAS  PubMed  Google Scholar 

  20. Luedde T, Schwabe RF. NF-kappaB in the liver–linking injury, fibrosis and hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2011;8(2):108–18.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Tai DI, Tsai SL, Chen YM, Chuang YL, Peng CY, Sheen IS, et al. Activation of nuclear factor kappaB in hepatitis C virus infection: implications for pathogenesis and hepatocarcinogenesis. Hepatology. 2000;31(3):656–64.

    Article  CAS  PubMed  Google Scholar 

  22. Albini A, Tosetti F, Benelli R, Noonan DM. Tumor inflammatory angiogenesis and its chemoprevention. Cancer Res. 2005;65(23):10637–41.

    Article  CAS  PubMed  Google Scholar 

  23. Scapini P, Morini M, Tecchio C, Minghelli S, Di Carlo E, Tanghetti E, et al. CXCL1/macrophage inflammatory protein-2-induced angiogenesis in vivo is mediated by neutrophil-derived vascular endothelial growth factor-A. J Immunol. 2004;172(8):5034–40.

    Article  CAS  PubMed  Google Scholar 

  24. Li YW, Qiu SJ, Fan J, Zhou J, Gao Q, Xiao YS, et al. Intratumoral neutrophils: a poor prognostic factor for hepatocellular carcinoma following resection. J Hepatol. 2011;54(3):497–505.

    Article  PubMed  Google Scholar 

  25. Gomez D, Farid S, Malik HZ, Young AL, Toogood GJ, Lodge JP, et al. Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative resection for hepatocellular carcinoma. World J Surg. 2008;32(8):1757–62.

    Article  CAS  PubMed  Google Scholar 

  26. Kuang DM, Zhao Q, Wu Y, Peng C, Wang J, Xu Z, et al. Peritumoral neutrophils link inflammatory response to disease progression by fostering angiogenesis in hepatocellular carcinoma. J Hepatol. 2011;54(5):948–55.

    Article  CAS  PubMed  Google Scholar 

  27. Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell. 2006;124(2):263–6.

    Article  CAS  PubMed  Google Scholar 

  28. Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004;4(1):71–8.

    Article  CAS  PubMed  Google Scholar 

  29. Movahedi K, Laoui D, Gysemans C, Baeten M, Stange G, Van den Bossche J, et al. Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Res. 2010;70(14):5728–39.

    Article  CAS  PubMed  Google Scholar 

  30. 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):1640–8.

    Article  CAS  PubMed  Google Scholar 

  31. Kuang DM, Zhao Q, Peng C, Xu J, Zhang JP, Wu 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):1327–37.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010;11(10):889–96.

    Article  CAS  PubMed  Google Scholar 

  33. Peng SH, Deng H, Yang JF, Xie PP, Li C, Li H, et al. Significance and relationship between infiltrating inflammatory cell and tumor angiogenesis in hepatocellular carcinoma tissues. World J Gastroenterol. 2005;11(41):6521–4.

    PubMed Central  PubMed  Google Scholar 

  34. Yang W, Lu Y, Xu Y, Xu L, Zheng W, Wu Y, et al. Estrogen represses hepatocellular carcinoma (HCC) growth via inhibiting alternative activation of tumor-associated macrophages (TAMs). J Biol Chem. 2012;287(48):40140–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Yang J, Zhang JX, Wang H, Wang GL, Hu QG, Zheng QC. Hepatocellular carcinoma and macrophage interaction induced tumor immunosuppression via Treg requires TLR4 signaling. World J Gastroenterol. 2012;18(23):2938–47.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Ju MJ, Qiu SJ, Fan J, Xiao YS, Gao Q, Zhou J, et al. Peritumoral activated hepatic stellate cells predict poor clinical outcome in hepatocellular carcinoma after curative resection. Am J Clin Pathol. 2009;131(4):498–510.

    Article  CAS  PubMed  Google Scholar 

  37. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299(5609):1057–61.

    Article  CAS  PubMed  Google Scholar 

  38. Mathai AM, Kapadia MJ, Alexander J, Kernochan LE, Swanson PE, Yeh MM. Role of Foxp3-positive tumor-infiltrating lymphocytes in the histologic features and clinical outcomes of hepatocellular carcinoma. Am J Surg Pathol. 2012;36(7):980–6.

    Article  PubMed  Google Scholar 

  39. Zhou L, Fu JL, Lu YY, Fu BY, Wang CP, An LJ, et al. Regulatory T cells are associated with post-cryoablation prognosis in patients with hepatitis B virus-related hepatocellular carcinoma. J Gastroenterol. 2010;45(9):968–78.

    Article  CAS  PubMed  Google Scholar 

  40. Lin GH, Wang J, Li SH, Xu L, Li SP. Relationship and clinical significance of TGF-beta1 expression with Treg cell infiltration in hepatocellular carcinoma. Chin J Cancer. 2010;29(4):403–7.

    Article  PubMed  Google Scholar 

  41. 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):1745–54.

    Article  CAS  PubMed  Google Scholar 

  42. Zhang HH, Mei MH, Fei R, Liu F, Wang JH, Liao WJ, et al. Regulatory T cells in chronic hepatitis B patients affect the immunopathogenesis of hepatocellular carcinoma by suppressing the anti-tumour immune responses. J Viral Hepat. 2010;17 Suppl 1:34–43.

    Article  PubMed  Google Scholar 

  43. Wu H, Chen P, Liao R, Li YW, Yi Y, Wang JX, et al. Intratumoral regulatory T cells with higher prevalence and more suppressive activity in HCC patients. J Gastroenterol Hepatol. 2013;28(9):1555–64.

    Article  CAS  PubMed  Google Scholar 

  44. Yi Y, He HW, Wang JX, Cai XY, Li YW, Zhou J, et al. The functional impairment of HCC-infiltrating gammadelta T cells, partially mediated by regulatory T cells in a TGFbeta- and IL-10-dependent manner. J Hepatol. 2013;58(5):977–83.

    Article  CAS  PubMed  Google Scholar 

  45. Kakita N, Kanto T, Itose I, Kuroda S, Inoue M, Matsubara T, et al. Comparative analyses of regulatory T cell subsets in patients with hepatocellular carcinoma: a crucial role of CD25(-) FOXP3(-) T cells. Int J Cancer. 2012;131(11):2573–83.

    Article  CAS  PubMed  Google Scholar 

  46. Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012;366(6):539–51.

    Article  CAS  PubMed  Google Scholar 

  47. Harada K, Shimoda S, Kimura Y, Sato Y, Ikeda H, Igarashi S, et al. Significance of immunoglobulin G4 (IgG4)-positive cells in extrahepatic cholangiocarcinoma: molecular mechanism of IgG4 reaction in cancer tissue. Hepatology. 2012;56(1):157–64.

    Article  CAS  PubMed  Google Scholar 

  48. Kimura Y, Harada K, Nakanuma Y. Pathologic significance of immunoglobulin G4-positive plasma cells in extrahepatic cholangiocarcinoma. Hum Pathol. 2012;43(12):2149–56.

    Article  CAS  PubMed  Google Scholar 

  49. Quezada SA, Peggs KS. Exploiting CTLA-4, PD-1 and PD-L1 to reactivate the host immune response against cancer. Br J Cancer. 2013;108(8):1560–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Ye Y, Zhou L, Xie X, Jiang G, Xie H, Zheng S. Interaction of B7-H1 on intrahepatic cholangiocarcinoma cells with PD-1 on tumor-infiltrating T cells as a mechanism of immune evasion. J Surg Oncol. 2009;100(6):500–4.

    Article  PubMed  Google Scholar 

  51. Hasita H, Komohara Y, Okabe H, Masuda T, Ohnishi K, Lei XF, et al. Significance of alternatively activated macrophages in patients with intrahepatic cholangiocarcinoma. Cancer Sci. 2010;101(8):1913–9.

    Article  CAS  PubMed  Google Scholar 

  52. Jarnagin WR. Management of small hepatocellular carcinoma: a review of transplantation, resection, and ablation. Ann Surg Oncol. 2010;17(5):1226–33.

    Article  PubMed Central  PubMed  Google Scholar 

  53. Truty MJ, Vauthey JN. Surgical resection of high-risk hepatocellular carcinoma: patient selection, preoperative considerations, and operative technique. Ann Surg Oncol. 2010;17(5):1219–25.

    Article  PubMed Central  PubMed  Google Scholar 

  54. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334(11):693–9.

    Article  CAS  PubMed  Google Scholar 

  55. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–90.

    Article  CAS  PubMed  Google Scholar 

  56. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10(1):25–34.

    Article  CAS  PubMed  Google Scholar 

  57. El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 2008;134(6):1752–63.

    Article  PubMed  Google Scholar 

  58. Park J, Kim MH, Kim KP, Park do H, Moon SH, Song TJ, et al. Natural history and prognostic factors of advanced cholangiocarcinoma without surgery, chemotherapy, or radiotherapy: a large-scale observational study. Gut Liver. 2009;3(4):298–305.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987;329(6139):506–12.

    Article  CAS  PubMed  Google Scholar 

  60. Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 1987;329(6139):512–8.

    Article  CAS  PubMed  Google Scholar 

  61. Rosenberg SA. Adoptive immunotherapy of cancer: accomplishments and prospects. Cancer Treat Rep. 1984;68(1):233–55.

    CAS  PubMed  Google Scholar 

  62. Unitt E, Marshall A, Gelson W, Rushbrook SM, Davies S, Vowler SL, et al. Tumour lymphocytic infiltrate and recurrence of hepatocellular carcinoma following liver transplantation. J Hepatol. 2006;45(2):246–53.

    Article  CAS  PubMed  Google Scholar 

  63. Cai L, Zhang Z, Zhou L, Wang H, Fu J, Zhang S, et al. Functional impairment in circulating and intrahepatic NK cells and relative mechanism in hepatocellular carcinoma patients. Clin Immunol. 2008;129(3):428–37.

    Article  CAS  PubMed  Google Scholar 

  64. Kwon S, Kim D, Park BK, Cho S, Kim KD, Kim YE, et al. Prevention and therapy of hepatocellular carcinoma by vaccination with TM4SF5 epitope-CpG-DNA-liposome complex without carriers. PLoS ONE. 2012;7(3):e33121.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Yi BR, Hwang KA, Kang NH, Kim SU, Jeung EB, Kim HC, et al. Synergistic effects of genetically engineered stem cells expressing cytosine deaminase and interferon-beta via their tumor tropism to selectively target human hepatocarcinoma cells. Cancer Gene Ther. 2012;19(9):644–51.

    Article  CAS  PubMed  Google Scholar 

  66. Gao J, Luo SM, Peng ML, Deng T. Enhanced immunity against hepatoma induced by dendritic cells pulsed with Hsp70-H22 peptide complexes and CD40L. J Cancer Res Clin Oncol. 2012;138(6):917–26.

    Article  CAS  PubMed  Google Scholar 

  67. Butterfield LH, Koh A, Meng W, Vollmer CM, Ribas A, Dissette V, et al. Generation of human T-cell responses to an HLA-A2.1-restricted peptide epitope derived from alpha-fetoprotein. Cancer Res. 1999;59(13):3134–42.

    CAS  PubMed  Google Scholar 

  68. Liu Y, Daley S, Evdokimova VN, Zdobinski DD, Potter DM, Butterfield LH. Hierarchy of alpha fetoprotein (AFP)-specific T cell responses in subjects with AFP-positive hepatocellular cancer. J Immunol. 2006;177(1):712–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Jakubovic BD, Jothy S. Glypican-3: from the mutations of Simpson-Golabi-Behmel genetic syndrome to a tumor marker for hepatocellular carcinoma. Exp Mol Pathol. 2007;82(2):184–9.

    Article  CAS  PubMed  Google Scholar 

  70. Shirakawa H, Kuronuma T, Nishimura Y, Hasebe T, Nakano M, Gotohda N, et al. Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer. Int J Oncol. 2009;34(3):649–56.

    CAS  PubMed  Google Scholar 

  71. Shirakawa H, Suzuki H, Shimomura M, Kojima M, Gotohda N, Takahashi S, et al. Glypican-3 expression is correlated with poor prognosis in hepatocellular carcinoma. Cancer Sci. 2009;100(8):1403–7.

    Article  CAS  PubMed  Google Scholar 

  72. Komori H, Nakatsura T, Senju S, Yoshitake Y, Motomura Y, Ikuta Y, et al. Identification of HLA-A2- or HLA-A24-restricted CTL epitopes possibly useful for glypican-3-specific immunotherapy of hepatocellular carcinoma. Clin Cancer Res. 2006;12(9):2689–97.

    Article  CAS  PubMed  Google Scholar 

  73. Sawada Y, Yoshikawa T, Nobuoka D, Shirakawa H, Kuronuma T, Motomura Y, et al. Phase I trial of a glypican-3-derived peptide vaccine for advanced hepatocellular carcinoma: immunologic evidence and potential for improving overall survival. Clin Cancer Res. 2012;18(13):3686–96.

    Article  CAS  PubMed  Google Scholar 

  74. Nobuoka D, Yoshikawa T, Sawada Y, Fujiwara T, Nakatsura T. Peptide vaccines for hepatocellular carcinoma. Hum Vaccin Immunother. 2013;9(1):210–2.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Yamamoto K, Ueno T, Kawaoka T, Hazama S, Fukui M, Suehiro Y, et al. MUC1 peptide vaccination in patients with advanced pancreas or biliary tract cancer. Anticancer Res. 2005;25(5):3575–9.

    CAS  PubMed  Google Scholar 

  76. El Ansary M, Mogawer S, Elhamid SA, Alwakil S, Aboelkasem F, Sabaawy HE, et al. Immunotherapy by autologous dendritic cell vaccine in patients with advanced HCC. J Cancer Res Clin Oncol. 2013;139(1):39–48.

    Article  PubMed  Google Scholar 

  77. Qiu Y, Xu MB, Yun MM, Wang YZ, Zhang RM, Meng XK, et al. Hepatocellular carcinoma-specific immunotherapy with synthesized alpha1,3- galactosyl epitope-pulsed dendritic cells and cytokine-induced killer cells. World J Gastroenterol. 2011;17(48):5260–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med. 1987;316(15):889–97.

    Article  CAS  PubMed  Google Scholar 

  79. Rosenberg SA, Yannelli JR, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, et al. Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. J Natl Cancer Inst. 1994;86(15):1159–66.

    Article  CAS  PubMed  Google Scholar 

  80. Stromnes IM, Fowler C, Casamina CC, Georgopolos CM, McAfee MS, Schmitt TM, et al. Abrogation of SRC homology region 2 domain-containing phosphatase 1 in tumor-specific T cells improves efficacy of adoptive immunotherapy by enhancing the effector function and accumulation of short-lived effector T cells in vivo. J Immunol. 2012;189(4):1812–25.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Morisaki T, Onishi H, Koya N, Kiyota A, Tanaka H, Umebayashi M, et al. Combinatorial cytotoxicity of gemcitabine and cytokine-activated killer cells in hepatocellular carcinoma via the NKG2D-MICA/B system. Anticancer Res. 2011;31(7):2505–10.

    CAS  PubMed  Google Scholar 

  82. Takayama T, Sekine T, Makuuchi M, Yamasaki S, Kosuge T, Yamamoto J, et al. Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial. Lancet. 2000;356(9232):802–7.

    Article  CAS  PubMed  Google Scholar 

  83. Zhong JH, Ma L, Wu LC, Zhao W, Yuan WP, Wu FX, et al. Adoptive immunotherapy for postoperative hepatocellular carcinoma: a systematic review. Int J Clin Pract. 2012;66(1):21–7.

    Article  PubMed  Google Scholar 

  84. Zhou P, Liang P, Dong B, Yu X, Han Z, Xu Y. Phase clinical study of combination therapy with microwave ablation and cellular immunotherapy in hepatocellular carcinoma. Cancer Biol Ther. 2011;11(5):450–6.

    Article  CAS  PubMed  Google Scholar 

  85. Zhu AX, Duda DG, Sahani DV, Jain RK. HCC and angiogenesis: possible targets and future directions. Nat Rev Clin Oncol. 2011;8(5):292–301.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  86. Garbi N, Arnold B, Gordon S, Hammerling GJ, Ganss R. CpG motifs as proinflammatory factors render autochthonous tumors permissive for infiltration and destruction. J Immunol. 2004;172(10):5861–9.

    Article  CAS  PubMed  Google Scholar 

  87. Boige V, Malka D, Bourredjem A, Dromain C, Baey C, Jacques N, et al. Efficacy, safety, and biomarkers of single-agent bevacizumab therapy in patients with advanced hepatocellular carcinoma. Oncologist. 2012;17(8):1063–72.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  88. Fang P, Hu JH, Cheng ZG, Liu ZF, Wang JL, Jiao SC. Efficacy and safety of bevacizumab for the treatment of advanced hepatocellular carcinoma: a systematic review of phase II trials. PLoS ONE. 2012;7(12):e49717.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  89. McCoy KD, Le Gros G. The role of CTLA-4 in the regulation of T cell immune responses. Immunol Cell Biol. 1999;77(1):1–10.

    Article  CAS  PubMed  Google Scholar 

  90. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  91. Mizukoshi E, Nakamoto Y, Arai K, Yamashita T, Sakai A, Sakai Y, et al. Comparative analysis of various tumor-associated antigen-specific t-cell responses in patients with hepatocellular carcinoma. Hepatology. 2011;53(4):1206–16.

    Article  CAS  PubMed  Google Scholar 

  92. Zhang Z, Bian H, Feng Q, Mi L, Mo T, Kuang A, et al. Biodistribution and localization of iodine-131-labeled metuximab in patients with hepatocellular carcinoma. Cancer Biol Ther. 2006;5(3):318–22.

    Article  CAS  PubMed  Google Scholar 

  93. Chen ZN, Mi L, Xu J, Song F, Zhang Q, Zhang Z, et al. Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (131I) metuximab injection: clinical phase I/II trials. Int J Radiat Oncol Biol Phys. 2006;65(2):435–44.

    Article  CAS  PubMed  Google Scholar 

  94. Xu J, Shen ZY, Chen XG, Zhang Q, Bian HJ, Zhu P, et al. A randomized controlled trial of Licartin for preventing hepatoma recurrence after liver transplantation. Hepatology. 2007;45(2):269–76.

    Article  CAS  PubMed  Google Scholar 

  95. Zhu H, Yang B, Yang X, Wang L, Xu J, Liao C, et al. A novel antibody fragment targeting HAb18G/CD147 with cytotoxicity and decreased immunogenicity. Cancer Biol Ther. 2009;8(11):1035–44.

    Article  CAS  PubMed  Google Scholar 

  96. The LO. Tapping our immune potential to realise the ultimate goal. Lancet Oncol. 2011;12(13):1175.

    Article  Google Scholar 

  97. Finn OJ. Cancer immunology. N Engl J Med. 2008;358(25):2704–15.

    Article  CAS  PubMed  Google Scholar 

  98. Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer. 2008;8(4):299–308.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  99. Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480(7378):480–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

The work is partially supported by grants from National Major Project of China (No.2011ZX09302-001-01), and National Natural Science Fund of China (81272684).

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  1. State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Guoxue Lane 37, Chengdu, 610041, China

    Zhen-Yu Ding MD & Yu-Quan Wei MD, PhD

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Correspondence to Yu-Quan Wei MD, PhD .

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  1. Children's Medical Center, Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran

    Nima Rezaei

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Ding, ZY., Wei, YQ. (2015). Immunopathology of Hepatobiliary Tumors and Immunotherapy of Liver Cancers. In: Rezaei, N. (eds) Cancer Immunology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46410-6_10

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  • DOI: https://doi.org/10.1007/978-3-662-46410-6_10

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-46409-0

  • Online ISBN: 978-3-662-46410-6

  • eBook Packages: MedicineMedicine (R0)

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