肝细胞癌中的免疫检查点阻断：当前进展与未来方向
Immune checkpoint blockade in hepatocellular carcinoma: current progress and future directions.
作者信息
Hato Tai, Goyal Lipika, Greten Tim F, Duda Dan G, Zhu Andrew X
机构信息
Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA.
出版信息
Hepatology. 2014 Nov;60(5):1776-82. doi: 10.1002/hep.27246. Epub 2014 Sep 26.
Abstract
Immune checkpoint blockade has recently emerged as a promising therapeutic approach for various malignancies including hepatocellular carcinoma (HCC). Preclinical and clinical studies have shown the potential benefit of modulating the immunogenicity of HCC. In addition, recent advances in tumor immunology have broadened our understanding of the complex mechanism of immune evasion. In this review we summarize the current knowledge on HCC immunology and discuss the potential of immune checkpoint blockade as a novel HCC therapy from the basic, translational, and clinical perspectives.
摘要
免疫检查点阻断最近已成为包括肝细胞癌（HCC）在内的各种恶性肿瘤的一种有前景的治疗方法。临床前和临床研究已显示出调节HCC免疫原性的潜在益处。此外，肿瘤免疫学的最新进展拓宽了我们对免疫逃逸复杂机制的理解。在本综述中，我们总结了目前关于HCC免疫学的知识，并从基础、转化和临床角度讨论免疫检查点阻断作为一种新型HCC治疗方法的潜力。
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J Gastroenterol. 2015 Jan;50(1):65-75. doi: 10.1007/s00535-014-0933-3. Epub 2014 Feb 8.
2
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