383
Views
13
CrossRef citations to date
0
Altmetric
Review

Immunotherapy of hepatocellular carcinoma

, , &
Pages 345-353 | Published online: 10 Jan 2014

References

  • Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J. Clin. Oncol.27(9), 1485–1491 (2009).
  • Greten TF, Papendorf F, Bleck JS et al. Survival rate in patients with hepatocellular carcinoma: a retrospective analysis of 389 patients. Br. J. Cancer92(10), 1862–1868 (2005).
  • Llovet JM, Ricci S, Mazzaferro V et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med.359(4), 378–390 (2008).
  • El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology134(6), 1752–1763 (2008).
  • Thomas MB, O’Beirne JP, Furuse J, Chan AT, Abou-Alfa G, Johnson P. Systemic therapy for hepatocellular carcinoma: cytotoxic chemotherapy, targeted therapy and immunotherapy. Ann. Surg. Oncol.15(4), 1008–1014 (2008).
  • Greten TF, Korangy F, Manns MP, Malek NP. Molecular therapy for the treatment of hepatocellular carcinoma. Br. J. Cancer100(1), 19–23 (2009).
  • Finn OJ. Cancer immunology. N. Engl. J. Med.358(25), 2704–2715 (2008).
  • Greten TF, Manns MP, Korangy F. Immunotherapy of HCC. Rev. Recent Clin. Trials3(1), 31–39 (2008).
  • Chang MH, Chen CJ, Lai MS et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N. Engl. J. Med.336(26), 1855–1859 (1997).
  • Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat. Rev. Immunol.5(3), 215–229 (2005).
  • Naugler WE, Sakurai T, Kim S et al. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science317(5834), 121–124 (2007).
  • Wada Y, Nakashima O, Kutami R, Yamamoto O, Kojiro M. Clinicopathological study on hepatocellular carcinoma with lymphocytic infiltration. Hepatology27(2), 407–414 (1998).
  • 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. Gastroenterology132(7), 2328–2339 (2007).
  • 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.25(18), 2586–2593 (2007).
  • Unitt E, Marshall A, Gelson W et al. Tumour lymphocytic infiltrate and recurrence of hepatocellular carcinoma following liver transplantation. J. Hepatol.45(2), 246–253 (2006).
  • Chew V, Tow C, Teo M et al. Inflammatory tumor microenvironment is associated with superior survival in hepatocellular carcinoma patients. J. Hepatol.52(3), 370–379 (2010).
  • Budhu A, Forgues M, Ye QH et al. Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment. Cancer Cell10(2), 99–111 (2006).
  • 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.15(3), 971–979 (2009).
  • Blondon H, Fritsch L, Cherqui D. Two cases of spontaneous regression of multicentric hepatocellular carcinoma after intraperitoneal rupture: possible role of immune mechanisms. Eur. J. Gastroenterol. Hepatol.16(12), 1355–1359 (2004).
  • Butterfield LH, Ribas A, Meng WS et al. T-cell responses to HLA-A*0201 immunodominant peptides derived from α-fetoprotein in patients with hepatocellular cancer. Clin. Cancer Res.9(16 Pt 1), 5902–5908 (2003).
  • Butterfield LH, Ribas A, Dissette VB et al. A Phase I/II trial testing immunization of hepatocellular carcinoma patients with dendritic cells pulsed with four α-fetoprotein peptides. Clin. Cancer Res.12(9), 2817–2825 (2006).
  • Butterfield LH, Ribas A, Potter DM, Economou JS. Spontaneous and vaccine induced AFP-specific T cell phenotypes in subjects with AFP-positive hepatocellular cancer. Cancer Immunol. Immunother.56(12), 1931–1943 (2007).
  • Kong J, Diao Z, Deng X, Zhong H, Yao W, Hu X. Anti-tumor effects of immunotherapeutic peptide on the treatment of hepatocellular carcinoma with HBc carrier. Oncol. Rep.18(1), 279–285 (2007).
  • Butterfield LH, Koh A, Meng W et al. Generation of human T-cell responses to an HLA-A2.1-restricted peptide epitope derived from α-fetoprotein. Cancer Res.59(13), 3134–3142 (1999).
  • Butterfield LH, Meng WS, Koh A et al. T cell responses to HLA-A*0201-restricted peptides derived from human a fetoprotein. J. Immunol.166(8), 5300–5308 (2001).
  • Meng WS, Butterfield LH, Ribas A et al. Fine specificity analysis of an HLA-A2.1-restricted immunodominant T cell epitope derived from human α-fetoprotein. Mol. Immunol.37(16), 943–950 (2000).
  • Mizukoshi E, Nakamoto Y, Tsuji H, Yamashita T, Kaneko S. Identification of α-fetoprotein-derived peptides recognized by cytotoxic T lymphocytes in HLA-A24+ patients with hepatocellular carcinoma. Int. J. Cancer118(5), 1194–1204 (2006).
  • Alisa A, Ives A, Pathan AA et al. Analysis of CD4+ T-cell responses to a novel α-fetoprotein-derived epitope in hepatocellular carcinoma patients. Clin. Cancer Res.11(18), 6686–6694 (2005).
  • Thimme R, Neagu M, Boettler T et al. Comprehensive analysis of the α-fetoprotein-specific CD8+ T cell responses in patients with hepatocellular carcinoma. Hepatology48(6), 1821–1833 (2008).
  • Bricard G, Bouzourene H, Martinet O et al. Naturally acquired MAGE-A10- and SSX-2-specific CD8+ T cell responses in patients with hepatocellular carcinoma. J. Immunol.174(3), 1709–1716 (2005).
  • Zhang HG, Chen HS, Peng JR et al. Specific CD8+ T cell responses to HLA-A2 restricted MAGE-A3 p271–279 peptide in hepatocellular carcinoma patients without vaccination. Cancer Immunol. Immunother.56(12), 1945–1954 (2007).
  • Riener MO, Wild PJ, Soll C et al. Frequent expression of the novel cancer testis antigen MAGE-C2/CT-10 in hepatocellular carcinoma. Int. J. Cancer124(2), 352–357 (2009).
  • Korangy F, Ormandy LA, Bleck JS et al. Spontaneous tumor-specific humoral and cellular immune responses to NY-ESO-1 in hepatocellular carcinoma. Clin. Cancer Res.10(13), 4332–4341 (2004).
  • Peng JR, Chen HS, Mou DC et al. Expression of cancer/testis (CT) antigens in Chinese hepatocellular carcinoma and its correlation with clinical parameters. Cancer Lett.219(2), 223–232 (2005).
  • Chen HS, Qin LL, Cong X et al. Expression of tumor-specific cancer/testis antigens in hepatocellular carcinoma. Zhonghua Gan Zang Bing Za Zhi11(3), 145–148 (2003).
  • Shang XY, Chen HS, Zhang HG et al. The spontaneous CD8+ T-cell response to HLA-A2-restricted NY-ESO-1b peptide in hepatocellular carcinoma patients. Clin. Cancer Res.10(20), 6946–6955 (2004).
  • Chen CH, Chen GJ, Lee HS et al. Expressions of cancer-testis antigens in human hepatocellular carcinomas. Cancer Lett.164(2), 189–195 (2001).
  • 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. Gastroenterology137(2), 682–690 (2009).
  • Vonderheide RH, Hahn WC, Schultze JL, Nadler LM. The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes. Immunity10(6), 673–679 (1999).
  • Miura N, Horikawa I, Nishimoto A et al. Progressive telomere shortening and telomerase reactivation during hepatocellular carcinogenesis. Cancer Genet. Cytogenet.93(1), 56–62 (1997).
  • Miura N, Maeda Y, Kanbe T et al. Serum human telomerase reverse transcriptase messenger RNA as a novel tumor marker for hepatocellular carcinoma. Clin. Cancer Res.11(9), 3205–3209 (2005).
  • Mizukoshi E, Nakamoto Y, Marukawa Y et al. Cytotoxic T cell responses to human telomerase reverse transcriptase in patients with hepatocellular carcinoma. Hepatology43(6), 1284–1294 (2006).
  • Nakamoto Y, Mizukoshi E, Tsuji H et al. Combined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellular carcinoma: clinical safety. Clin. Exp. Immunol.147(2), 296–305 (2007).
  • Hiroishi K, Eguchi J, Baba T et al. Strong CD8+ T-cell responses against tumor-associated antigens prolong the recurrence-free interval after tumor treatment in patients with hepatocellular carcinoma. J. Gastroenterol.45(4), 451–458 (2009).
  • Sakaguchi S, Powrie F. Emerging challenges in regulatory T cell function and biology. Science317(5838), 627–629 (2007).
  • 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. Cancer125(7), 1640–1648 (2009).
  • Knutson KL, Disis ML, Salazar LG. CD4 regulatory T cells in human cancer pathogenesis. Cancer Immunol. Immunother.56(3), 271–285 (2007).
  • Audia S, Nicolas A, Cathelin D et al. Increase of CD4+ CD25+ regulatory T cells in the peripheral blood of patients with metastatic carcinoma: a Phase I clinical trial using cyclophosphamide and immunotherapy to eliminate CD4+ CD25+ T lymphocytes. Clin. Exp. Immunol.150(3), 523–530 (2007).
  • 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.65(6), 2457–2464 (2005).
  • Unitt E, Rushbrook SM, Marshall A et al. Compromised lymphocytes infiltrate hepatocellular carcinoma: the role of T-regulatory cells. Hepatology41(4), 722–730 (2005).
  • 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.45(2), 254–262 (2006).
  • Chen W, Jin W, Hardegen N et al. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3. J. Exp. Med.198(12), 1875–1886 (2003).
  • Yamaguchi R, Yano H, Iemura A, Ogasawara S, Haramaki M, Kojiro M. Expression of vascular endothelial growth factor in human hepatocellular carcinoma. Hepatology28(1), 68–77 (1998).
  • Beckebaum S, Zhang X, Chen X et al. Increased levels of interleukin-10 in serum from patients with hepatocellular carcinoma correlate with profound numerical deficiencies and immature phenotype of circulating dendritic cell subsets. Clin. Cancer Res.10(21), 7260–7269 (2004).
  • Giannelli G, Fransvea E, Marinosci F et al. Transforming growth factor-β1 triggers hepatocellular carcinoma invasiveness via α3β1 integrin. Am. J. Pathol.161(1), 183–193 (2002).
  • Shimizu J, Yamazaki S, Sakaguchi S. Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J. Immunol.163(10), 5211–5218 (1999).
  • Golgher D, Jones E, Powrie F, Elliott T, Gallimore A. Depletion of CD25+ regulatory cells uncovers immune responses to shared murine tumor rejection antigens. Eur. J. Immunol.32(11), 3267–3275 (2002).
  • Shimizu K, Fields RC, Giedlin M, Mule JJ. Systemic administration of interleukin 2 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines. Proc. Natl Acad. Sci. USA96(5), 2268–2273 (1999).
  • Ghiringhelli F, Larmonier N, Schmitt E et al. CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur. J. Immunol.34(2), 336–344 (2004).
  • Dannull J, Su Z, Rizzieri D et al. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J. Clin. Invest.115(12), 3623–3633 (2005).
  • Greten TF, Ormandy L, 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.33(2), 211–218 (2010).
  • Gabrilovich D. Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat. Rev. Immunol.4(12), 941–952 (2004).
  • Gabrilovich DI, Corak J, Ciernik IF, Kavanaugh D, Carbone DP. Decreased antigen presentation by dendritic cells in patients with breast cancer. Clin. Cancer Res.3(3), 483–490 (1997).
  • Ishida T, Oyama T, Carbone DP, Gabrilovich DI. Defective function of Langerhans cells in tumor-bearing animals is the result of defective maturation from hemopoietic progenitors. J. Immunol.161(9), 4842–4851 (1998).
  • Ormandy LA, Farber A, Cantz T et al. Direct ex vivo analysis of dendritic cells in patients with hepatocellular carcinoma. World J. Gastroenterol.12(20), 3275–3282 (2006).
  • Kakumu S, Ito S, Ishikawa T et al. Decreased function of peripheral blood dendritic cells in patients with hepatocellular carcinoma with hepatitis B and C virus infection. J. Gastroenterol. Hepatol.15(4), 431–436 (2000).
  • Ninomiya T, Akbar SM, Masumoto T, Horiike N, Onji M. Dendritic cells with immature phenotype and defective function in the peripheral blood from patients with hepatocellular carcinoma. J. Hepatol.31(2), 323–331 (1999).
  • Chen S, Akbar SM, Tanimoto K et al. Absence of CD83-positive mature and activated dendritic cells at cancer nodules from patients with hepatocellular carcinoma: relevance to hepatocarcinogenesis. Cancer Lett.148(1), 49–57 (2000).
  • Tang TJ, Vukosavljevic D, Janssen HL et al. Aberrant composition of the dendritic cell population in hepatic lymph nodes of patients with hepatocellular carcinoma. Hum. Pathol.37(3), 332–338 (2006).
  • Gabrilovich DI, Ishida T, Nadaf S, Ohm JE, Carbone DP. Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function. Clin. Cancer Res.5(10), 2963–2970 (1999).
  • Gabrilovich D, Ishida T, Oyama T et al. Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood92(11), 4150–4166 (1998).
  • Ohm JE, Shurin MR, Esche C, Lotze MT, Carbone DP, Gabrilovich DI. Effect of vascular endothelial growth factor and FLT3 ligand on dendritic cell generation in vivo. J. Immunol.163(6), 3260–3268 (1999).
  • Menetrier-Caux C, Montmain G, Dieu MC et al. Inhibition of the differentiation of dendritic cells from CD34+ progenitors by tumor cells: role of interleukin-6 and macrophage colony-stimulating factor. Blood92(12), 4778–4791 (1998).
  • Ratta M, Fagnoni F, Curti A et al. Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6. Blood100(1), 230–237 (2002).
  • Park SJ, Nakagawa T, Kitamura H et al. IL-6 regulates in vivo dendritic cell differentiation through STAT3 activation. J. Immunol.173(6), 3844–3854 (2004).
  • Yang AS, Lattime EC. Tumor-induced interleukin 10 suppresses the ability of splenic dendritic cells to stimulate CD4 and CD8 T-cell responses. Cancer Res.63(9), 2150–2157 (2003).
  • Beissert S, Hosoi J, Grabbe S, Asahina A, Granstein RD. IL-10 inhibits tumor antigen presentation by epidermal antigen-presenting cells. J. Immunol.154(3), 1280–1286 (1995).
  • Steinbrink K, Graulich E, Kubsch S, Knop J, Enk AH. CD4+ and CD8+ anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity. Blood99(7), 2468–2476 (2002).
  • Um SH, Mulhall C, Alisa A et al. α-fetoprotein impairs APC function and induces their apoptosis. J. Immunol.173(3), 1772–1778 (2004).
  • Pak AS, Wright MA, Matthews JP, Collins SL, Petruzzelli GJ, Young MR. Mechanisms of immune suppression in patients with head and neck cancer: presence of CD34+ cells which suppress immune functions within cancers that secrete granulocyte-macrophage colony-stimulating factor. Clin. Cancer Res.1(1), 95–103 (1995).
  • Almand B, Clark JI, Nikitina E et al. Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J. Immunol.166(1), 678–689 (2001).
  • Serafini P, Borrello I, Bronte V. Myeloid suppressor cells in cancer: recruitment, phenotype, properties, and mechanisms of immune suppression. Semin. Cancer Biol.16(1), 53–65 (2006).
  • Zea AH, Rodriguez PC, Atkins MB et al. Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res.65(8), 3044–3048 (2005).
  • Filipazzi P, Valenti R, Huber V et al. Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J. Clin. Oncol.25(18), 2546–2553 (2007).
  • Serafini P, Meckel K, Kelso M et al. Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J. Exp. Med.203(12), 2691–2702 (2006).
  • Mirza N, Fishman M, Fricke I et al. All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res.66(18), 9299–9307 (2006).
  • Smyth MJ, Crowe NY, Hayakawa Y, Takeda K, Yagita H, Godfrey DI. NKT cells – conductors of tumor immunity? Curr. Opin. Immunol.14(2), 165–171 (2002).
  • Smyth MJ, Wallace ME, Nutt SL, Yagita H, Godfrey DI, Hayakawa Y. Sequential activation of NKT cells and NK cells provides effective innate immunotherapy of cancer. J. Exp. Med.201(12), 1973–1985 (2005).
  • 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.129(3), 428–437 (2008).
  • 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. Hepatology50(3), 799–807 (2009).
  • Subleski JJ, Hall VL, Back TC, Ortaldo JR, Wiltrout RH. Enhanced antitumor response by divergent modulation of natural killer and natural killer T cells in the liver. Cancer Res.66(22), 11005–11012 (2006).
  • Tsuchiyama T, Nakamoto Y, Sakai Y et al. Prolonged, NK cell-mediated antitumor effects of suicide gene therapy combined with monocyte chemoattractant protein-1 against hepatocellular carcinoma. J. Immunol.178(1), 574–583 (2007).
  • Bricard G, Cesson V, Devevre E et al. Enrichment of human CD4+ V(a)24/Vb11 invariant NKT cells in intrahepatic malignant tumors. J. Immunol.182(8), 5140–5151 (2009).
  • Takikawa O, Yoshida R, Kido R, Hayaishi O. Tryptophan degradation in mice initiated by indoleamine 2,3-dioxygenase. J. Biol. Chem.261(8), 3648–3653 (1986).
  • Munn DH, Mellor AL. Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J. Clin. Invest.117(5), 1147–1154 (2007).
  • Pan K, Wang H, Chen MS et al. Expression and prognosis role of indoleamine 2,3-dioxygenase in hepatocellular carcinoma. J. Cancer Res. Clin. Oncol.134(11), 1247–1253 (2008).
  • Ishio T, Goto S, Tahara K, Tone S, Kawano K, Kitano S. Immunoactivative role of indoleamine 2,3-dioxygenase in human hepatocellular carcinoma. J. Gastroenterol. Hepatol.19(3), 319–326 (2004).
  • Cheng AS, Chan HL, To KF et al. Cyclooxygenase-2 pathway correlates with vascular endothelial growth factor expression and tumor angiogenesis in hepatitis B virus-associated hepatocellular carcinoma. Int. J. Oncol.24(4), 853–860 (2004).
  • Tang TC, Poon RT, Lau CP, Xie D, Fan ST. Tumor cyclooxygenase-2 levels correlate with tumor invasiveness in human hepatocellular carcinoma. World J. Gastroenterol.11(13), 1896–1902 (2005).
  • Wolff H, Saukkonen K, Anttila S, Karjalainen A, Vainio H, Ristimaki A. Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res.58(22), 4997–5001 (1998).
  • Taketo MM. Cyclooxygenase-2 inhibitors in tumorigenesis (part II). J. Natl Cancer Inst.90(21), 1609–1620 (1998).
  • Taketo MM. Cyclooxygenase-2 inhibitors in tumorigenesis (part I). J. Natl Cancer Inst.90(20), 1529–1536 (1998).
  • Iwamoto A, Ikeguchi M, Matsumoto S et al. Tumor cyclooxygenase-2 gene suppresses local immune responses in patients with hepatocellular carcinoma. Tumori92(2), 130–133 (2006).
  • Palmer DH, Midgley RS, Mirza N et al. A Phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma. Hepatology49(1), 124–132 (2009).
  • Mizukoshi E, Nakamoto Y, Arai K et al. Enhancement of tumor-specific T cell responses by transcatheter arterial embolization with dendritic cell infusion for hepatocellular carcinoma. Int. J. Cancer126(9), 2164–2174 (2010).
  • Zerbini A, Pilli M, Fagnoni F et al. Increased immunostimulatory activity conferred to antigen-presenting cells by exposure to antigen extract from hepatocellular carcinoma after radiofrequency thermal ablation. J. Immunother.31(3), 271–282 (2008).
  • Ali MY, Grimm CF, Ritter M et al. Activation of dendritic cells by local ablation of hepatocellular carcinoma. J. Hepatol.43(5), 817–822 (2005).
  • Zerbini A, Pilli M, Laccabue D et al. Radiofrequency thermal ablation for hepatocellular carcinoma stimulates autologous NK-cell response. Gastroenterology138(5), 1931–1942 (2010).
  • Zerbini A, Pilli M, Penna A et al. Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses. Cancer Res.66(2), 1139–1146 (2006).
  • Ayaru L, Pereira SP, Alisa A et al. Unmasking of α-fetoprotein-specific CD4+ T cell responses in hepatocellular carcinoma patients undergoing embolization. J. Immunol.178(3), 1914–1922 (2007).
  • Ji J, Shi J, Budhu A et al. MicroRNA expression, survival, and response to interferon in liver cancer. N. Engl. J. Med.361(15), 1437–1447 (2009).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.