Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois.
The Jackson Laboratory Cancer Center, Bar Harbor, Maine.
Cancer Discov. 2018 Nov;8(11):1358-1365. doi: 10.1158/2159-8290.CD-18-0044. Epub 2018 Oct 11.
Immunotherapy has revolutionized cancer therapy, largely attributed to the success of immune-checkpoint blockade. However, there are subsets of patients across multiple cancers who have not shown robust responses to these agents. A major impediment to progress in the field is the availability of faithful mouse models that recapitulate the complexity of human malignancy and immune contexture within the tumor microenvironment. These models are urgently needed across all malignancies to interrogate and predict antitumor immune responses and therapeutic efficacy in clinical trials. Herein, we seek to review pros and cons of different cancer mouse models, and how they can be used as platforms to predict efficacy and resistance to cancer immunotherapies. Although immunotherapy has shown substantial benefit in the treatment of a variety of malignancies, a key hurdle toward the advancement of these therapies is the availability of immunocompetent preclinical mouse models that recapitulate human disease. Here, we review the evolution of preclinical mouse models and their utility as coclinical platforms for mechanistic interrogation of cancer immunotherapies.
免疫疗法极大地改变了癌症治疗方式,这主要归因于免疫检查点阻断的成功。然而,在多种癌症中,仍有一部分患者对这些药物没有明显的反应。该领域进展的主要障碍是缺乏能够重现肿瘤微环境中人类恶性肿瘤和免疫结构复杂性的忠实于人类的小鼠模型。在所有癌症中都迫切需要这些模型,以在临床试验中探究和预测抗肿瘤免疫反应和治疗效果。本文中,我们旨在综述不同癌症小鼠模型的优缺点,以及它们如何作为平台来预测癌症免疫疗法的疗效和耐药性。尽管免疫疗法在治疗多种恶性肿瘤方面显示出了显著的益处,但这些疗法的进一步发展的一个关键障碍是缺乏能够重现人类疾病的免疫活性的临床前小鼠模型。在这里,我们综述了临床前小鼠模型的发展及其作为癌症免疫疗法的机制研究的共临床平台的应用。