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免疫检查点能否成为治疗特发性肺纤维化的有效靶点?

Immune Checkpoints as Promising Targets for the Treatment of Idiopathic Pulmonary Fibrosis?

作者信息

Duitman JanWillem, van den Ende Tom, Spek C Arnold

机构信息

Amsterdam UMC, Center for Experimental and Molecular Medicine, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

Amsterdam UMC, Department of Medical Oncology, Cancer Center Amsterdam, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

出版信息

J Clin Med. 2019 Sep 26;8(10):1547. doi: 10.3390/jcm8101547.

Abstract

Idiopathic pulmonary fibrosis is a rare, progressive and fatal lung disease which affects approximately 5 million persons worldwide. Although pirfenidone and/or nintedanib treatment improves patients' wellbeing, the prognosis of IPF remains poor with 5-year mortality rates still ranging from 70 to 80%. The promise of the anti-cancer agent nintedanib in IPF, in combination with the recent notion that IPF shares several pathogenic pathways with cancer, raised hope that immune checkpoint inhibitors, the novel revolutionary anticancer agents, could also be the eagerly awaited ground-breaking and unconventional novel treatment modality limiting IPF-related morbidity/mortality. In the current review, we analyse the available literature on immune checkpoint proteins in IPF to explore whether immune checkpoint inhibition may be as promising in IPF as it is in cancer. We conclude that despite several promising papers showing that inhibiting specific immune checkpoint proteins limits pulmonary fibrosis, overall the data seem to argue against a general role of immune checkpoint inhibition in IPF and suggest that only PD-1/PD-L1 inhibition may be beneficial.

摘要

特发性肺纤维化是一种罕见、进行性且致命的肺部疾病,全球约有500万人受其影响。尽管吡非尼酮和/或尼达尼布治疗可改善患者的健康状况,但特发性肺纤维化的预后仍然很差,5年死亡率仍在70%至80%之间。抗癌药物尼达尼布在特发性肺纤维化治疗中的应用前景,以及最近关于特发性肺纤维化与癌症具有多种共同致病途径的观点,让人们燃起了希望,即免疫检查点抑制剂这种新型的革命性抗癌药物,也可能成为备受期待的、突破性的非常规新型治疗方式,以限制与特发性肺纤维化相关的发病率/死亡率。在本综述中,我们分析了有关特发性肺纤维化中免疫检查点蛋白的现有文献,以探讨免疫检查点抑制在特发性肺纤维化中是否可能像在癌症中一样具有前景。我们得出的结论是,尽管有几篇很有前景的论文表明,抑制特定的免疫检查点蛋白可限制肺纤维化,但总体而言,数据似乎并不支持免疫检查点抑制在特发性肺纤维化中具有普遍作用的观点,并表明只有抑制PD-1/PD-L1可能有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfbe/6833050/f298e630b9ba/jcm-08-01547-g001.jpg

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