基于免疫治疗肝癌患者目前的概念：从基础科学到新的治疗

StephenW

  Gut doi:10.1136/gutjnl-2014-307990

    Recent advances in clinical practice

Current concepts of immune based treatments for patients with HCC: from basic science to novel treatment approaches

    Tim F Greten 1,
    Xin W Wang 2,
    Firouzeh Korangy 1

+ Author Affiliations

    1 Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
    2 Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, USA

    Correspondence to Professor Tim F Greten, Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH/NCI/CCR Building 10 Rm. 12N226, 9000 Rockville Pike, Bethesda, MD 20892, USA; [email protected]

    Received 23 November 2014
    Revised 9 January 2015
    Accepted 12 January 2015
    Published Online First 9 February 2015

Abstract

The recent approval of two immune checkpoint inhibitors for the treatment of malignant melanoma has sparked great interest by physicians and basic scientists searching for novel therapeutics for GI cancer. Chronic inflammation is recognised as a major risk factor for the development of hepatocellular carcinoma (HCC) and makes this type of cancer a potentially ideal target for an immune based treatment approach. Further evidence for a critical role of immune responses in patients with HCC is derived from the fact that immune signatures and profiles predict patients’ outcome as well as the fact that tumour-induced spontaneous antitumour immunity can be detected. In addition ablative therapies can lead to changes in the number, phenotype and function of different immune cell subsets, which correlate with patients’ survival. Various HCC-specific mouse models have been developed, which improve our understanding of hepatocarcinogenesis and tumour-immune cell interactions, and lead to the development of novel immune based treatment approaches, which are currently being evaluated in preclinical and in early clinical settings. Immune checkpoint blockade along with adoptive immune cell therapy and vaccine approaches are currently being evaluated either alone or in combination with other treatments. Here, we provide an overview for the rationale of immunotherapy in HCC, summarise ongoing studies and provide a perspective for immune based approaches in patients with HCC.

StephenW

肠道DOI：10.1136/ gutjnl-2014-307990

    在临床实践中的最新进展

基于免疫治疗肝癌患者目前的概念：从基础科学到新的治疗方法

    蒂姆˚FGreten1，
    鑫W¯¯王2，
    Firouzeh Korangy1

+作者所属机构

    1胃肠道恶性肿瘤科，胸胃肠肿瘤科，癌症研究中心，国家癌症研究所，美国国立卫生研究院，马里兰州贝塞斯达，USA
    2肝癌发生部分，人类致癌，癌症研究中心，国家癌症研究所，美国国立卫生研究院，贝塞斯达，美国实验室

    对应教授蒂姆˚FGreten，胃肠道恶性肿瘤科，胸胃肠肿瘤科，癌症研究中心，国家癌症研究所，美国国立卫生研究院/ NCI/ CCR大厦10室。 12N226，9000罗克维尔派克贝塞斯达，MD20892，USA; [email protected]

    收到的2014年11月23日
    修订后的2015年1月9日
    接受2015年1月12日
    网上公布第一2015年2月9日

摘要

两种免疫检查点抑制剂对恶性黑色素瘤的治疗，最近的批准引发了医生和基础科学家寻找新的治疗癌症的GI极大的兴趣。慢性炎症被认为是肝细胞癌（HCC）的发展的主要危险因素，使得这种类型的癌症为基础的免疫治疗方法潜在的理想目标。对免疫应答的患者的HCC关键作用的进一步证据从这一事实免疫签名和型材预测患者的预后以及肿瘤诱导的自发的抗肿瘤免疫力，可检测出的事实得出。除了烧蚀疗法可以导致改变的数目，表型和不同的免疫细胞亚群，这与患者的生存率相关的功能。各种肝癌特异性小鼠模型已经被开发，这对提高我们的肝癌发生和肿瘤的免疫细胞相互作用的理解，并导致新的基于免疫的治疗方法，这是目前在临床前和早期临床环境评估的发展。随着过继免疫细胞疗法和疫苗方法免疫检查点封锁目前正在评估单独或与其他治疗结合。这里，我们提供了用于免疫治疗肝癌的理由的概述，总结正在进行的研究和基于免疫的方法在肝癌患者提供的立体。