Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Review Article

Can Combined Therapy Benefit Immune Checkpoint Blockade Response in Hepatocellular Carcinoma?

Author(s): Fan Zhongqi, Sun Xiaodong, Chen Yuguo and Lv Guoyue*

Volume 19, Issue 2, 2019

Page: [222 - 228] Pages: 7

DOI: 10.2174/1871520618666181114112431

Price: $65

Abstract

Background: Hepatocellular Carcinoma (HCC) is one of the most common cancers with high mortality rate. The effects of most therapies are limited. The Immune Checkpoint Blockade (ICB) improves the prognosis in multiple malignancies. The application of immune checkpoint blockade to hepatocellular carcinoma patients has recently started. Early phase clinical trials have shown some benefits to cancer patients.

Methods/Results: This review focuses on the immune system of liver and clinical trials of ICB. In particular, we analyze the mechanisms by which immune checkpoint blockade therapies can be used for the treatment of hepatocellular carcinoma patients, then examine the factors in cancer resistance to the therapies and finally suggest possible combination therapies for the treatment of hepatocellular carcinoma patients.

Conclusion: ICB is a promising therapy for advanced HCC patients. Combined therapy exhibits a great potential to enhance ICB response in these patients. The better understanding of the factors influencing the sensitivity of ICB and more clinical trials will consolidate the efficiency and minimize the adverse effects of ICB.

Keywords: Hepatocellular carcinoma, immune checkpoint blockade, immune response, combined therapy, tumor microenvironment, immunogenic cell death.

Graphical Abstract

[1]
Chen, W.Q.; Zheng, R.S.; Zhang, S.W. Report of cancer incidence and mortality in China 2012. Chin. Cancer, 2016, 2(7), 61-61.
[2]
Moriguchi, M.; Umemura, A.; Itoh, Y. Current status and future prospects of chemotherapy for advanced hepatocellular carcinoma. Clin. J. Gastroenterol., 2016, 9(4), 1-7.
[3]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics. Cancer J. Clin., 2015, 64(1), 9-29.
[4]
Postow, M.A.; Harding, J.; Wolchok, J.D. Targeting immune checkpoints: Releasing the restraints on anti-tumor immunity for patients with melanoma. Cancer J., 2012, 18(2), 153-159.
[5]
Zhou, F.; Teng, F.; Deng, P.; Meng, N.; Song, Z.; Feng, R. Recent progress of nano-drug delivery system for liver cancer treatment. Anticancer. Agents Med. Chem., 2018, 17(14), 1884-1897.
[6]
Hodi, F.S.; O’Day, S.J.; McDermott, D.F.; Weber, R.W.; Sosman, J.A.; Haanen, J.B.; Gonzalez, R.; Robert, C.; Schadendorf, D.; Hassel, J.C.; Akerley, W.; van den Eertwegh, A.J.; Lutzky, J.; Lorigan, P.; Vaubel, J.M.; Linette, G.P.; Hogg, D.; Ottensmeier, C.H.; Lebbe, C.; Peschel, C.; Quirt, I.; Clark, J.I.; Wolchok, J.D.; Weber, J.S.; Tian, J.; Yellin, M.J.; Nichol, G.M.; Hoos, A.; Urba, W.J. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med., 2010, 363(8), 711-723.
[7]
Marra, A.; Ferrone, C.; Fusciello, C.; Scognamiglio, G.; Ferrone, S.; Pepe, S.; Perri, F.; Sabbatino, F. Translational research in cutaneous melanoma: New therapeutic perspectives. Anticancer. Agents Med. Chem., 2017, 18(2), 166-181.
[8]
Zou, W.; Wolchok, J.D.; Chen, L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations. Sci. Transl. Med., 2016, 8(328), 328rv4- 328rv4.
[9]
Helissey, C.; Vicier, C.; Champiat, S. The development of immunotherapy in older adults: New treatments, new toxicities? J. Geriatr. Oncol., 2016, 7(5), 325-333.
[10]
Bang, Y-J.; Chung, H-C.; Shankaran, V.; Geva, R.; Catenacci, D.V.T.; Gupta, S.; Eder, J.P.; Berger, R.; Gonzalez, E.J.; Ray, A. Relationship between PD-L1 expression and clinical outcomes in patients with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) in KEYNOTE- 012. ASCO. Ann. Meet. Proc, 2015, 33, 4001.
[11]
Hamanishi, J.; Mandai, M.; Ikeda, T.; Minami, M.; Kawaguchi, A.; Matsumura, N.; Abiko, K.; Baba, T.; Yamaguchi, K.; Ueda, A. Durable tumor remission in patients with platinum-resistant ovarian cancer receiving nivolumab. Ann. Meet. Proc, 2015, 5570.
[12]
Emens, L.A.; Braiteh, F.S.; Cassier, P.; Delord, J.P.; Eder, J.P.; Fasso, M.; Xiao, Y.; Wang, Y.; Molinero, L.; Chen, D.S. Abstract 2859: Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic Triple-Negative Breast Cancer (TNBC). Cancer Res., 2015, 75(9)(Suppl.), 2589.
[13]
Le, D.T.; Uram, J.N.; Wang, H.; Bartlett, B.R.; Kemberling, H.; Eyring, A.D.; Skora, A.D.; Luber, B.S.; Azad, N.S.; Laheru, D.; Biedrzycki, B.; Donehower, R.C.; Zaheer, A.; Fisher, G.A.; Crocenzi, T.S.; Lee, J.J.; Duffy, S.M.; Goldberg, R.M.; de la Chapelle, A.; Koshiji, M.; Bhaijee, F.; Huebner, T.; Hruban, R.H.; Wood, L.D.; Cuka, N.; Pardoll, D.M.; Papadopoulos, N.; Kinzler, K.W.; Zhou, S.; Cornish, T.C.; Taube, J.M.; Anders, R.A.; Eshleman, J.R.; Vogelstein, B.; Diaz, L.A., Jr PD-1 blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med., 2015, 372(26), 2509-2520.
[14]
Elkhoueiry, A.B.; Melero, I.; Crocenzi, T.S.; Welling, T.H.; Yau, T.C.; Yeo, W.; Chopra, A.; Grosso, J.; Lang, L.; Anderson, J. Phase I/II safety and antitumor activity of nivolumab in patients with advanced hepatocellular carcinoma (HCC): CA209-040. J. Clin. Oncol., 2015, 33(18)(Suppl.)
[15]
Ansell, S.M.; Lesokhin, A.M.; Borrello, I.; Halwani, A.; Scott, E.C.; Gutierrez, M.; Schuster, S.J.; Millenson, M.M.; Cattry, D.; Freeman, G.J. PD-1 Blockade with nivolumab in relapsed or refractory hodgkin’s lymphoma. N. Engl. J. Med., 2015, 372(4), 311-319.
[16]
Prieto, J.; Melero, I.; Sangro, B. Immunological landscape and immunotherapy of hepatocellular carcinoma. Nat. Rev. Gastroenterol. Hepatol., 2015, 12(12), 681-700.
[17]
Poisson, J.; Lemoinne, S.; Boulanger, C.; Durand, F.; Moreau, R.; Valla, D.; Rautou, P.E. Liver sinusoidal endothelial cells: Physiology and role in liver diseases. J. Hepatol., 2017, 66(1), 212-227.
[18]
Knolle, P.A.; Uhrig, A.; Hegenbarth, S.; Löser, E.; Schmitt, E.; Gerken, G.; Lohse, A.W. IL-10 down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells through decreased antigen uptake via the mannose receptor and lowered surface expression of accessory molecules. Clin. Exp. Immunol., 1998, 114(3), 427-433.
[19]
Katz, S.C.; Pillarisetty, V.G.; Bleier, J.I.; Shah, A.B.; Dematteo, R.P. Liver sinusoidal endothelial cells are insufficient to activate T cells. J. Immunol., 2004, 173(1), 230-235.
[20]
Limmer, A.; Ohl, J.; Kurts, C.; Ljunggren, H.G.; Reiss, Y.; Groettrup, M.; Momburg, F.; Arnold, B.; Knolle, P.A. Efficient presentation of exogenous antigen by liver endothelial cells to CD8+ T cells results in antigen-specific T-cell tolerance. Nat. Med., 2000, 6(12), 1348-1354.
[21]
Diehl, L.; Schurich, A.; Grochtmann, R.; Hegenbarth, S.; Chen, L.; Knolle, P.A. Tolerogenic maturation of liver sinusoidal endothelial cells promotes B7-homolog 1-dependent CD8+ T cell tolerance. Hepatology, 2008, 47(1), 296-305.
[22]
Carambia, A.; Freund, B.; Schwinge, D.; Heine, M.; Laschtowitz, A.; Huber, S.; Wraith, D.C.; Korn, T.; Schramm, C.; Lohse, A.W.; Heeren, J.; Herkel, J. TGF-beta-dependent induction of CD4(+)CD25(+)Foxp3(+) Tregs by liver sinusoidal endothelial cells. J. Hepatol., 2014, 61(3), 594-599.
[23]
Neumann, K.; Rudolph, C.; Neumann, C.; Janke, M.; Amsen, D.; Scheffold, A. Liver sinusoidal endothelial cells induce immunosuppressive IL-10-producing Th1 cells via the Notch pathway. Eur. J. Immunol., 2015, 45(7), 2008-2016.
[24]
Weiskirchen, R.; Tacke, F. Cellular and molecular functions of hepatic stellate cells in inflammatory responses and liver immunology. Hepatobiliary Surg. Nutr., 2014, 3(6), 344-363.
[25]
Chang, J.; Hisamatsu, T.; Shimamura, K.; Yoneno, K.; Adachi, M.; Naruse, H.; Igarashi, T.; Higuchi, H.; Matsuoka, K.; Kitazume, M.T.; Ando, S.; Kamada, N.; Kanai, T.; Hibi, T. Activated hepatic stellate cells mediate the differentiation of macrophages. Hepatol. Res., 2013, 43(6), 658-669.
[26]
Schildberg, F.A.; Wojtalla, A.; Siegmund, S.V.; Endl, E.; Diehl, L.; Abdullah, Z.; Kurts, C.; Knolle, P.A. Murine hepatic stellate cells veto CD8 T cell activation by a CD54-dependent mechanism. Hepatology, 2011, 54(1), 262-272.
[27]
Holt, A.P.; Haughton, E.L.; Lalor, P.F.; Filer, A.; Buckley, C.D.; Adams, D.H. Liver myofibroblasts regulate infiltration and positioning of lymphocytes in human liver. Gastroenterology, 2009, 136(2), 705-714.
[28]
Maher, J.J. Interactions between hepatic stellate cells and the immune system. Semin. Liver Dis., 2001, 21(3), 417-426.
[29]
Yang, H.R.; Chou, H.S.; Gu, X.; Wang, L.; Brown, K.E.; Fung, J.J.; Lu, L.; Qian, S. Mechanistic insights into immunomodulation by hepatic stellate cells in mice: A critical role of interferon-gamma signaling. Hepatology, 2009, 50(6), 1981-1991.
[30]
Yu, M.C.; Chen, C.H.; Liang, X.; Wang, L.; Gandhi, C.R.; Fung, J.J.; Lu, L.; Qian, S. Inhibition of T-cell responses by hepatic stellate cells via B7-H1-mediated T-cell apoptosis in mice. Hepatology, 2004, 40(6), 1312-1321.
[31]
Heymann, F.; Tacke, F. Immunology in the liver - from homeostasis to disease. Nat. Rev. Gastroenterol. Hepatol., 2016, 13(2), 88.
[32]
Tacke, F.; Zimmermann, H.W. Macrophage heterogeneity in liver injury and fibrosis. J. Hepatol., 2014, 60(5), 1090-1096.
[33]
Garcia-Rubino, M.E.; Lozano-Lopez, C.; Campos, J.M. Inhibitors of cancer stem cells. Anticancer. Agents Med. Chem., 2016, 16(10), 1230-1239.
[34]
Heymann, F.; Peusquens, J.; Ludwig‐Portugall, I.; Kohlhepp, M.; Ergen, C.; Niemietz, P.; Martin, C.; Rooijen, N.V.; Ochando, J.C.; Randolph, G.J. Liver inflammation abrogates immunological tolerance induced by Kupffer cells. Hepatology, 2015, 62(1), 279-291.
[35]
Knoll, P.; Schlaak, J.; Uhrig, A.; Kempf, P.; Gerken, G. Human Kupffer cells secrete IL-10 in response to Lipopolysaccharide (LPS) challenge. J. Hepatol., 1995, 22(2), 226-229.
[36]
Callery, M.P.; Mangino, M.J.; Flye, M.W. Arginine-specific suppression of mixed lymphocyte culture reactivity by Kupffer cells--a basis of portal venous tolerance. Transplantation, 1991, 51(5), 1076-1080.
[37]
Li, S.; Yang, F.; Ren, X. Immunotherapy for hepatocellular carcinoma. Drug Discov. Ther., 2015, 9(5), 363-371.
[38]
Harding, J.J.; El, D.I.; Aboualfa, G.K. Immunotherapy in hepatocellular carcinoma: Primed to make a difference? Cancer, 2016, 122(3), 367-377.
[39]
Pardoll, D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer, 2012, 12(4), 252-264.
[40]
Wen, X.; Long, F.J.; Xiao, Z.D.; Dan, Y.Z.; Jia, P.P.; Mao, L.X.; Bing, J.L.; Chang, J.W.; Jing, H.Z.; Qi, Z. PD-1/PD-L1 signal pathway participates in HCV F protein-induced T cell dysfunction in chronic HCV infection. Immunol. Res., 2016, 64(2), 1-12.
[41]
Schurich, A.; Khanna, P.; Lopes, A.R.; Han, K.J.; Peppa, D.; Micco, L.; Nebbia, G.; Kennedy, P.T.; Geretti, A.M.; Dusheiko, G. Role of the coinhibitory receptor cytotoxic T lymphocyte antigen-4 on apoptosis-Prone CD8 T cells in persistent hepatitis B virus infection. Hepatology, 2011, 53(5), 1494-1503.
[42]
Bengsch, B.; Martin, B.; Thimme, R. Restoration of HBV-specific CD8+ T cell function by PD-1 blockade in inactive carrier patients is linked to T cell differentiation. J. Hepatol., 2014, 61(6), 1212-1219.
[43]
Tzeng, H.T.; Tsai, H.F.; Liao, H.J.; Lin, Y.J.; Chen, L.; Chen, P.J.; Hsu, P.N. PD-1 Blockage reverses immune dysfunction and hepatitis b viral persistence in a mouse animal model. PLoS One, 2012, 7(6), 76-77.
[44]
Ye, B.; Liu, X.; Li, X.; Kong, H.; Tian, L.; Chen, Y. T-cell exhaustion in chronic hepatitis B infection: Current knowledge and clinical significance. Cell Death Dis., 2015, 6(3), e1694.
[45]
Calderaro, J.; Rousseau, B.; Amaddeo, G.; Mercey, M.; Charpy, C.; Costentin, C.; Luciani, A.; Zafrani, E.S.; Laurent, A.; Azoulay, D.; Lafdil, F. Programmed death ligand 1 expression in hepatocellular carcinoma: Relationship with clinical and pathological features. Hepatology (Baltimore, Md.), 2016, 64(6), 2038-2046.
[46]
Cariani, E.; Pilli, M.; Zerbini, A.; Rota, C.; Olivani, A.; Pelosi, G.; Schianchi, C.; Soliani, P.; Campanini, N.; Silini, E.M. Immunological and molecular correlates of disease recurrence after liver resection for hepatocellular carcinoma. PLoS One, 2012, 7(3), e32493.
[47]
Zhen, Z.; Feng, S.; Lin, Z.; Zhang, M.N.; Yan, C.; Chang, X.J.; Lu, Y.Y.; Bai, W.L.; Qu, J.H.; Wang, C.P. Upregulation of Circulating PD-L1/PD-1 Is Associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma. PLoS One, 2011, 6(9), e23621.
[48]
Gao, Q.; Wang, X.Y.; Qiu, S.J.; Yamato, I.; Sho, M.; Nakajima, Y.; Zhou, J.; Li, B.Z. Shi, Y.H.; Xiao, Y.S.; Xu, Y. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin. Cancer Res., 2009, 15(3), 971-979.
[49]
Wu, K.; Kryczek, I.; Chen, L.; Zou, W.; Welling, T.H. Kupffer cell suppression of CD8+ T cells in human hepatocellular carcinoma is mediated by B7-H1/PD-1 interactions. Cancer Res., 2009, 69(20), 8067-8075.
[50]
Kuang, D.M.; Zhao, Q.; Peng, C.; Xu, J.; Zhang, J.P.; Wu, C.; Zheng, L. 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.
[51]
Kalathil, S.; Lugade, A.A.; Miller, A.; Iyer, R.; Thanavala, Y. Higher frequencies of GARP+ CTLA-4+ Foxp3+ T regulatory cells and myeloid-derivedsuppressor cells in hepatocellular carcinoma patients are associated with impaired T cellfunctionality. Cancer Res., 2013, 73(8), 2435-2444.
[52]
Wu, H.; Chen, P.; Liao, R.; Li, Y.W.; Yi, Y.; Wang, J.X.; Cai, X.Y.; He, H.W.; Jin, J.J.; Cheng, Y.F.; Fan, J.; Sun, J.; Qiu, S.J. Intratumoral regulatory T cells with higher prevalence and more suppressive activity in hepatocellular carcinoma patients. J. Gastroenterol. Hepatol., 2013, 28(9), 1555-1564.
[53]
Pitt, J.M.; Vetizou, M.; Daillere, R.; Roberti, M.P.; Yamazaki, T.; Routy, B.; Lepage, P.; Boneca, I.G.; Chamaillard, M.; Kroemer, G.; Zitvogel, L. Resistance mechanisms to immune-checkpoint blockade in cancer: Tumor-intrinsic and -extrinsic factors. Immunity, 2016, 44(6), 1255-1269.
[54]
Sharma, P.; Allison, J.P. Immune checkpoint targeting in cancer therapy: Toward combination strategies with curative potential. Cell, 2015, 161(2), 205-214.
[55]
Sangro, B.; Gomez-Martin, C.; de la Mata, M.; Inarrairaegui, M.; Garralda, E.; Barrera, P.; Riezu-Boj, J.I.; Larrea, E.; Alfaro, C.; Sarobe, P.; Lasarte, J.J.; Perez-Gracia, J.L.; Melero, I.; Prieto, J. 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.
[56]
Hanson, D.C.; Canniff, P.C.; Primiano, M.J.; Donovan, C.B.; Gardner, J.P.; Natoli, E.J.; Morgan, R.W.; Mather, R.J.; Singleton, D.H.; Hermes, P.A. Preclinical in vitro characterization of anti-CTLA4 therapeutic antibody CP-675,206. Cancer Res., 2004, 64(1), 877.
[57]
Canniff, P.C.; Donovan, C.B.; Burkwit, J.J.; Bruns, M.J.; Bedian, V.; Bernstein, S.H.; Hanson, D.C. CP-675,206 anti-CTLA4 antibody clinical candidate enhances IL-2 production in cancer patient T cells in vitro regardless of tumor type or stage of disease. Cancer Res., 2004, 64(1), 164.
[58]
Walker, L.S.; Sansom, D.M. The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses. Nat. Rev. Immunol., 2011, 11(12), 852-863.
[59]
Cominanduix, B.; Escuinordinas, H.; Ibarrondo, F.J. Tremelimumab: Research and clinical development. Oncotarget Ther, 2016, 9, 1767-1776.
[60]
Ribas, A.; Kefford, R.; Marshall, M.A.; Punt, C.J.; Haanen, J.B.; Marmol, M.; Garbe, C.; Gogas, H.; Schachter, J.; Linette, G.; Lorigan, P.; Kendra, K.L.; Maio, M.; Trefzer, U.; Smylie, M.; McArthur, G.A.; Dreno, B.; Nathan, P.D.; Mackiewicz, J.; Kirkwood, J.M.; Gomez-Navarro, J.; Huang, B.; Pavlov, D.; Hauschild, A. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J. Clin. Oncol., 2013, 31(5), 616-622.
[61]
Ascierto, P.A.; Pa, A. Is there still a role for tremelimumab in the treatment of cancer? Transl. Cancer Res., 2013, 2(1), 48-50.
[62]
Zhu, A.X.; Abrams, T.A.; Miksad, R.; Blaszkowsky, L.S.; Meyerhardt, J.A.; Zheng, H.; Muzikansky, A.; Clark, J.W.; Kwak, E.L.; Schrag, D.; Jors, K.R.; Fuchs, C.S.; Iafrate, A.J.; Borger, D.R.; Ryan, D.P. Phase 1/2 study of everolimus in advanced hepatocellular carcinoma. Cancer, 2011, 117(22), 5094-5102.
[63]
Park, J.W.; Finn, R.S.; Kim, J.S.; Karwal, M.; Li, R.K.; Ismail, F.; Thomas, M.; Harris, R.; Baudelet, C.; Walters, I.; Raoul, J.L. Phase II, open-label study of brivanib as first-line therapy in patients with advanced hepatocellular carcinoma. Clin. Cancer Res., 2011, 17(7), 1973-1983.
[64]
Therasse, P.; Arbuck, S.G.; Eisenhauer, E.A.; Wanders, J.; Kaplan, R.S.; Rubinstein, L.; Verweij, J.; Van Glabbeke, M.; van Oosterom, A.T.; Christian, M.C.; Gwyther, S.G. New guidelines to evaluate the response to treatment in solid tumors. J. Natl. Cancer Inst., 2000, 92(3), 205-216.
[65]
Wolchok, J.D.; Hoos, A.; O’Day, S.; Weber, J.S.; Hamid, O.; Lebbe, C.; Maio, M.; Binder, M.; Bohnsack, O.; Nichol, G.; Humphrey, R.; Hodi, F.S. Guidelines for the evaluation of immune therapy activity in solid tumors: Immune-related response criteria. Clin. Cancer Res., 2009, 15(23), 7412-7420.
[66]
Quezada, S.A.; Peggs, K.S. Exploiting CTLA-4, PD-1 and PD-L1 to reactivate the host immune response against cancer. Br. J. Cancer, 2013, 108(8), 1560-1565.
[67]
Dong, H.; Strome, S.E.; Salomao, D.R.; Tamura, H.; Hirano, F.; Flies, D.B.; Roche, P.C.; Lu, J.; Zhu, G.; Tamada, K.; Lennon, V.A.; Celis, E.; Chen, L. Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat. Med., 2002, 8(8), 793-800.
[68]
Segal, N.H.; Antonia, S.J.; Brahmer, J.R.; Maio, M.; Blakehaskins, A.; Li, X.; Vasselli, J.; Ibrahim, R.A.; Lutzky, J.; Khleif, S. Preliminary data from a multi-arm expansion study of MEDI4736, an anti-PD-L1 antibody. J. Clin. Oncol., 2014, 32, 3002.
[69]
Taube, J.M.; Klein, A.; Brahmer, J.R.; Xu, H.; Pan, X.; Kim, J.H.; Chen, L.; Pardoll, D.M.; Topalian, S.L.; Anders, R.A. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin. Cancer Res., 2014, 20(19), 5064-5074.
[70]
Larkin, J.; Chiarion-Sileni, V.; Gonzalez, R.; Grob, J.J.; Cowey, C.L.; Lao, C.D.; Schadendorf, D.; Dummer, R.; Smylie, M.; Rutkowski, P.; Ferrucci, P.F.; Hill, A.; Wagstaff, J.; Carlino, M.S.; Haanen, J.B.; Maio, M.; Marquez-Rodas, I.; McArthur, G.A.; Ascierto, P.A.; Long, G.V.; Callahan, M.K.; Postow, M.A.; Grossmann, K.; Sznol, M.; Dreno, B.; Bastholt, L.; Yang, A.; Rollin, L.M.; Horak, C.; Hodi, F.S.; Wolchok, J.D. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med., 2015, 373(1), 23-34.
[71]
Ngiow, S.F.; Young, A.; Jacquelot, N.; Yamazaki, T.; Enot, D.; Zitvogel, L.; Smyth, M.J. A threshold level of intratumor CD8+ T-cell PD1 expression dictates therapeutic response to anti-PD1. Cancer Res., 2015, 75(18), 3800-3811.
[72]
Penaloza-MacMaster, P.; Kamphorst, A.O.; Wieland, A.; Araki, K.; Iyer, S.S.; West, E.E.; O’Mara, L.; Yang, S.; Konieczny, B.T.; Sharpe, A.H.; Freeman, G.J.; Rudensky, A.Y.; Ahmed, R. Interplay between regulatory T cells and PD-1 in modulating T cell exhaustion and viral control during chronic LCMV infection. J. Exp. Med., 2014, 211(9), 1905-1918.
[73]
Onishi, H.; Morisaki, T.; Katano, M. Immunotherapy approaches targeting regulatory T-cells. Anticancer Res., 2012, 32(3), 997-1003.
[74]
Coussens, L.M.; Zitvogel, L.; Palucka, A.K. Neutralizing tumor-promoting chronic inflammation: A magic bullet? Science, 2013, 339(6117), 286-291.
[75]
Mittal, D.; Gubin, M.M.; Schreiber, R.D.; Smyth, M.J. New insights into cancer immunoediting and its three component phases--elimination, equilibrium and escape. Curr. Opin. Immunol., 2014, 27, 16-25.
[76]
Sharpe, A.H.; Wherry, E.J.; Ahmed, R.; Freeman, G.J. The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat. Immunol., 2007, 8(3), 239-245.
[77]
Bald, T.; Landsberg, J.; Lopez-Ramos, D.; Renn, M.; Glodde, N.; Jansen, P.; Gaffal, E.; Steitz, J.; Tolba, R.; Kalinke, U.; Limmer, A.; Jonsson, G.; Holzel, M.; Tuting, T. Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation. Cancer Discov., 2014, 4(6), 674-687.
[78]
Tarhini, A.A.; Cherian, J.; Moschos, S.J.; Tawbi, H.A.; Shuai, Y.; Gooding, W.E.; Sander, C.; Kirkwood, J.M. Safety and efficacy of combination immunotherapy with interferon alfa-2b and tremelimumab in patients with stage IV melanoma. J. Clin. Oncol., 2012, 30(3), 322-328.
[79]
Chen, L.T.; Chen, M.F.; Li, L.A.; Lee, P.H.; Jeng, L.B.; Lin, D.Y.; Wu, C.C.; Mok, K.T.; Chen, C.L.; Lee, W.C.; Chau, G.Y.; Chen, Y.S.; Lui, W.Y.; Hsiao, C.F.; Whang-Peng, J.; Chen, P.J. Long-term results of a randomized, observation-controlled, phase III trial of adjuvant interferon Alfa-2b in hepatocellular carcinoma after curative resection. Ann. Surg., 2012, 255(1), 8-17.
[80]
Arina, A.; Corrales, L.; Bronte, V. Enhancing T cell therapy by overcoming the immunosuppressive tumor microenvironment. Semin. Immunol., 2016, 28(1), 54-63.
[81]
Johansson, A.; Hamzah, J.; Payne, C.J.; Ganss, R. Tumor-targeted TNFalpha stabilizes tumor vessels and enhances active immunotherapy. Proc. Natl. Acad. Sci. USA, 2012, 109(20), 7841-7846.
[82]
Chauhan, V.P.; Jain, R.K. Strategies for advancing cancer nanomedicine. Nat. Mater., 2013, 12(11), 958-962.
[83]
Salnikova, O.; Breuhahn, K.; Hartmann, N.; Schmidt, J.; Ryschich, E. Endothelial plasticity governs the site-specific leukocyte recruitment in hepatocellular cancer. Int. J. Cancer, 2013, 133(10), 2372-2382.
[84]
Huang, Y.; Yuan, J.; Righi, E.; Kamoun, W.S.; Ancukiewicz, M.; Nezivar, J.; Santosuosso, M.; Martin, J.D.; Martin, M.R.; Vianello, F.; Leblanc, P.; Munn, L.L.; Huang, P.; Duda, D.G.; Fukumura, D.; Jain, R.K.; Poznansky, M.C. Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proc. Natl. Acad. Sci. USA, 2012, 109(43), 17561-17566.
[85]
Nadal, R.; Amin, A.; Geynisman, D.M.; Voss, M.H.; Weinstock, M.; Doyle, J.; Zhang, Z.; Viudez, A.; Plimack, E.R.; McDermott, D.F.; Motzer, R.; Rini, B.; Hammers, H.J. Safety and clinical activity of Vascular Endothelial Growth Factor Receptor (VEGFR)-tyrosine kinase inhibitors after programmed cell death 1 inhibitor treatment in patients with metastatic clear cell renal cell carcinoma. Ann. Oncol., 2016, 27(7), 1304-1311.
[86]
Amin, A.; Plimack, E.R.; Infante, J.R.; Ernstoff, M.S.; Rini, B.I.; McDermott, D.F.; Knox, J.J.; Pal, S.K.; Voss, M.H.; Sharma, P.; Kollmannsberger, C.K. Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with sunitinib or pazopanib in patients (pts) with metastatic renal cell carcinoma (mRCC). Ann. Meet. Proc., 2014, 2032, p. 5010..
[87]
Ohri, N.; Kaubisch, A.; Garg, M.; Guha, C. Targeted therapy for hepatocellular carcinoma. Semin. Radiat. Oncol., 2016, 26(4), 338-343.
[88]
Bhayani, N.H.; Jiang, Y.; Hamed, O.; Kimchi, E.T.; Staveley-O’Carroll, K.F.; Gusani, N.J. Advances in the pharmacologic treatment of hepatocellular carcinoma. Curr. Clin. Pharmacol., 2015, 10(4), 299-304.
[89]
Weiss, A.; van Beijnum, J.R.; Bonvin, D.; Jichlinski, P.; Dyson, P.J.; Griffioen, A.W.; Nowak-Sliwinska, P. Low-dose angiostatic tyrosine kinase inhibitors improve photodynamic therapy for cancer: lack of vascular normalization. J. Cell. Mol. Med., 2014, 18(3), 480-491.
[90]
Hato, T.; Zhu, A.X.; Duda, D.G. Rationally combining anti-VEGF therapy with checkpoint inhibitors in hepatocellular carcinoma. Immunotherapy, 2016, 8(3), 299-313.
[91]
Yaguchi, T.; Goto, Y.; Kido, K.; Mochimaru, H.; Sakurai, T.; Tsukamoto, N.; Kudo-Saito, C.; Fujita, T.; Sumimoto, H.; Kawakami, Y. Immune suppression and resistance mediated by constitutive activation of Wnt/beta-catenin signaling in human melanoma cells. J. Immunol., 2012, 189(5), 2110-2117.
[92]
Spranger, S.; Bao, R.; Gajewski, T.F. Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity. Nature, 2015, 523(7559), 231-235.
[93]
Zhong, Z.; Sanchez-Lopez, E.; Karin, M. Autophagy, Inflammation, and immunity: A troika governing cancer and its treatment. Cell, 2016, 166(2), 288-298.
[94]
Kroemer, G.; Galluzzi, L.; Kepp, O.; Zitvogel, L. Immunogenic cell death in cancer therapy. Immunology, 2013, 31(31), 224-233.
[95]
Martins, I.; Michaud, M.; Sukkurwala, A.Q.; Adjemian, S.; Ma, Y.; Shen, S.; Kepp, O.; Menger, L.; Vacchelli, E.; Galluzzi, L.; Zitvogel, L.; Kroemer, G. Premortem autophagy determines the immunogenicity of chemotherapy-induced cancer cell death. Autophagy, 2012, 8(3), 413-415.
[96]
Martinez-Lopez, N.; Athonvarangkul, D.; Singh, R. Autophagy and Aging; Springer: New York, 2015.
[97]
Malhi, H.; Kaufman, R.J. Endoplasmic Reticulum Stress in Liver Disease. J. Hepatol., 2011, 54(4), 795-809.
[98]
Pol, J.; Vacchelli, E.; Aranda, F.; Castoldi, F.; Eggermont, A.; Cremer, I.; Sautes-Fridman, C.; Fucikova, J.; Galon, J.; Spisek, R.; Tartour, E.; Zitvogel, L.; Kroemer, G.; Galluzzi, L. Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy. OncoImmunology, 2015, 4(4), e1008866.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy