Immuno-Oncology in Hepatocellular Carcinoma: 2017 Update

被引:83
作者
Kudo, Masatoshi [1 ]
机构
[1] Kindai Univ, Fac Med, Dept Gastroenterol & Hepatol, 377-2 Ohno Higashi, Osakasayama, Osaka 5898511, Japan
关键词
Hepatocellular carcinoma; Nivolumab; Pembrolizumab; Ipilimumab; Tremelimumab; CHECKPOINT INHIBITORS; ANTI-PD-L1; ANTIBODY; CLINICAL IMPACT; LIVER-CANCER; DOUBLE-BLIND; RECURRENCE; THERAPY; BLOCKADE; IPILIMUMAB; NIVOLUMAB;
D O I
10.1159/000481245
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Clinical trials are currently ongoing to evaluate the utility of antibodies against programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) as monotherapy or combination therapy in patients with hepatocellular carcinoma (HCC). Results of combination treatment with the anti-PD-L1 antibody durvalumab and the anti-CTLA-4 antibody tremelimumab in HCC were presented at the 2017 annual meeting of the ASCO (American Society of Clinical Oncology). Response rates were 25% in all 40 patients and 40% in the 20 uninfected patients, both of which are encouraging. Transcatheter arterial chemoembolization and radiofrequency ablation can activate tumor immunogenicity by releasing tumor-associated antigen and by inducing the migration of cytotoxic T lymphocytes to small intrahepatic metastatic nodules. Subsequent administration of anti-PD-1 antibody could control these small intrahepatic metastatic nodules. In a nonclinical study, the combination of pembrolizumab and lenvatinib inhibited the cancer immunosuppressive environments induced by tumor-associated macrophages and regulatory T cells. This, in turn, decreased the levels of TGF-beta and IL-10, the expression of PD-1, and the inhibition of Tim-3, triggering anticancer immunity mediated by immunostimulatory cytokines such as IL-12. Studies such as these may provide insight into the appropriate molecular targeted agents to be used with immune checkpoint inhibitors. (c) 2017 S. Karger AG, Basel
引用
收藏
页码:147 / 159
页数:13
相关论文
共 47 条
[1]  
[Anonymous], J CLIN ONCOL S, DOI DOI 10.1200/JCO.2017.35.15_suppl.4013
[2]  
[Anonymous], J CLIN ONCOL S
[3]   Effectiveness of Sorafenib in Patients with Transcatheter Arterial Chemoembolization (TACE) Refractory and Intermediate-Stage Hepatocellular Carcinoma [J].
Arizumi, Tadaaki ;
Ueshima, Kazuomi ;
Minami, Tomohiro ;
Kono, Masashi ;
Chishina, Hirokazu ;
Takita, Masahiro ;
Kitai, Satoshi ;
Inoue, Tatsuo ;
Yada, Norihisa ;
Hagiwara, Satoru ;
Minami, Yasunori ;
Sakurai, Toshiharu ;
Nishida, Naoshi ;
Kudo, Masatoshi .
LIVER CANCER, 2015, 4 (04) :253-262
[4]   Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer [J].
Brahmer, Julie R. ;
Tykodi, Scott S. ;
Chow, Laura Q. M. ;
Hwu, Wen-Jen ;
Topalian, Suzanne L. ;
Hwu, Patrick ;
Drake, Charles G. ;
Camacho, Luis H. ;
Kauh, John ;
Odunsi, Kunle ;
Pitot, Henry C. ;
Hamid, Omid ;
Bhatia, Shailender ;
Martins, Renato ;
Eaton, Keith ;
Chen, Shuming ;
Salay, Theresa M. ;
Alaparthy, Suresh ;
Grosso, Joseph F. ;
Korman, Alan J. ;
Parker, Susan M. ;
Agrawal, Shruti ;
Goldberg, Stacie M. ;
Pardoll, Drew M. ;
Gupta, Ashok ;
Wigginton, Jon M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (26) :2455-2465
[5]   Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial [J].
Bruix, Jordi ;
Takayama, Tadatoshi ;
Mazzaferro, Vincenzo ;
Chau, Gar-Yang ;
Yang, Jiamei ;
Kudo, Masatoshi ;
Cai, Jianqiang ;
Poon, Ronnie T. ;
Han, Kwang-Hyub ;
Tak, Won Young ;
Lee, Han Chu ;
Song, Tianqiang ;
Roayaie, Sasan ;
Bolondi, Luigi ;
Lee, Kwan Sik ;
Makuuchi, Masatoshi ;
Souza, Fabricio ;
Le Berre, Marie-Aude ;
Meinhardt, Gerold ;
Llovet, Josep M. .
LANCET ONCOLOGY, 2015, 16 (13) :1344-1354
[6]   Oncology Meets Immunology: The Cancer-Immunity Cycle [J].
Chen, Daniel S. ;
Mellman, Ira .
IMMUNITY, 2013, 39 (01) :1-10
[7]   Clinical impact of programmed cell death ligand 1 expression in colorectal cancer [J].
Droeser, Raoul A. ;
Hirt, Christian ;
Viehl, Carsten T. ;
Frey, Daniel M. ;
Nebiker, Christian ;
Huber, Xaver ;
Zlobec, Inti ;
Eppenberger-Castori, Serenella ;
Tzankov, Alexander ;
Rosso, Raffaele ;
Zuber, Markus ;
Muraro, Manuele Giuseppe ;
Amicarella, Francesca ;
Cremonesi, Eleonora ;
Heberer, Michael ;
Iezzi, Giandomenica ;
Lugli, Alessandro ;
Terracciano, Luigi ;
Sconocchia, Giuseppe ;
Oertli, Daniel ;
Spagnoli, Giulio C. ;
Tornillo, Luigi .
EUROPEAN JOURNAL OF CANCER, 2013, 49 (09) :2233-2242
[8]   Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma [J].
Duffy, Austin G. ;
Ulahannan, Susanna V. ;
Makorova-Rusher, Oxana ;
Rahma, Osama ;
Wedemeyer, Heiner ;
Pratt, Drew ;
Davis, Jeremy L. ;
Hughes, Marybeth S. ;
Heller, Theo ;
ElGindi, Mei ;
Uppala, Ashish ;
Korangy, Firouzeh ;
Kleiner, David E. ;
Figg, William D. ;
Venzon, David ;
Steinberg, Seth M. ;
Venkatesan, Aradhana M. ;
Krishnasamy, Venkatesh ;
Abi-Jaoudeh, Nadine ;
Levy, Elliot ;
Wood, Brad J. ;
Greten, Tim F. .
JOURNAL OF HEPATOLOGY, 2017, 66 (03) :545-551
[9]   Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial [J].
El-Khoueiry, Anthony B. ;
Sangro, Bruno ;
Yau, Thomas ;
Crocenzi, Todd S. ;
Kudo, Masatoshi ;
Hsu, Chiun ;
Kim, Tae-You ;
Choo, Su-Pin ;
Trojan, Jorg ;
Welling, Theodore H., III ;
Meyer, Tim ;
Kang, Yoon-Koo ;
Yeo, Winnie ;
Chopra, Akhil ;
Anderson, Jeffrey ;
dela Cruz, Christine ;
Lang, Lixin ;
Neely, Jaclyn ;
Tang, Hao ;
Dastani, Homa B. ;
Melero, Ignacio .
LANCET, 2017, 389 (10088) :2492-2502
[10]   Overexpression of PD-L1 Significantly Associates with Tumor Aggressiveness and Postoperative Recurrence in Human Hepatocellular Carcinoma [J].
Gao, Qiang ;
Wang, Xiao-Ying ;
Qiu, Shuang-Jian ;
Yamato, Ichiro ;
Sho, Masayuki ;
Nakajima, Yoshiyuki ;
Zhou, Jian ;
Li, Bai-Zhou ;
Shi, Ying-Hong ;
Xiao, Yong-Sheng ;
Xu, Yang ;
Fan, Jia .
CLINICAL CANCER RESEARCH, 2009, 15 (03) :971-979