Mouse Models of Oncoimmunology in Hepatocellular Carcinoma.
Mouse Models of Oncoimmunology in Hepatocellular Carcinoma.
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DOI：
10.1158/1078-0432.ccr-19-2923
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发表时间：
2020-10-15
期刊：
影响因子：
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通讯作者：
Lujambio A
中科院分区：
文献类型：
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作者：
Bresnahan E;Lindblad KE;Ruiz de Galarreta M;Lujambio A
肝癌是世界范围内癌症相关死亡的第四大原因，并且发病率正在上升。HCC是最常见的肝癌形式，具有复杂的病因和有限的治疗选择。晚期HCC患者的标准治疗是索拉非尼，这是一种酪氨酸激酶抑制剂，提供有限的生存益处。在过去的几年中，治疗晚期HCC的治疗选择大幅增加，包括额外的多激酶抑制剂以及免疫检查点抑制剂。Nivolumab和pembrolizumab分别于2017年和2018年获批作为晚期HCC的二线治疗药物。这些药物都靶向程序性死亡-1（PD-1）通路，表现出前所未有的结果，客观缓解率约为20%。然而，大多数患者没有反应，因此需要鉴定对免疫疗法的反应和抗性的生物标志物。随着免疫疗法在肿瘤学中的最近成功，需要更好地再现人类疾病和抗肿瘤免疫应答的小鼠模型。这篇综述列出了正在进行的肝癌免疫治疗临床试验，简要讨论了肝脏独特的免疫抑制环境，然后深入研究了目前最适用的小鼠模型系统，以研究肝癌背景下的肿瘤免疫学，包括同基因，基因工程和人源化模型。
Liver cancer is the fourth-leading cause of cancer-related mortality worldwide and incidence is on the rise. HCC is the most common form of liver cancer, with a complex etiology and limited treatment options. The standard of care treatment for advanced HCC patients is sorafenib, a tyrosine kinase inhibitor that offers limited survival benefit. In the past years, therapeutic options for the treatment of advanced HCC have increased substantially, including additional multikinase inhibitors as well as immune-checkpoint inhibitors. Nivolumab and pembrolizumab were approved in 2017 and 2018, respectively, as second-line treatment in advanced HCC. These drugs, both targeting the programmed death-1 (PD-1) pathway, demonstrate unprecedented results, with objective response rates of approximately 20%. However, the majority of patients do not respond, necessitating the identification of biomarkers of response and resistance to immunotherapy. With the recent success of immunotherapies in oncology, mouse models that better recapitulate the human disease and anti-tumor immune response are needed. This review lists ongoing clinical trials testing immunotherapy in HCC, briefly discusses the unique immunosuppressive environment of the liver, then delves into the most applicable current murine model systems to study oncoimmunology within the context of HCC, including syngeneic, genetically-engineered, and humanized models.