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PD-1/PD-L1 阻断作为结直肠癌的一种新治疗方法。

PD-1/ PD-L1 blockade as a novel treatment for colorectal cancer.

机构信息

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Biomed Pharmacother. 2019 Feb;110:312-318. doi: 10.1016/j.biopha.2018.11.105. Epub 2018 Dec 3.

Abstract

Colorectal cancer (CRC), as a prominent cause of cancer-related deaths, has historically been notable worldwide and many attempts have been made to raise the overall survival of CRC patients. Immune response has long been a question of great interest in a wide range of fields such as cancer therapies and anti-tumor immunity through checkpoint inhibitors, specifically anti PD-1/ PD-L1 interaction, is a new line of research for treatment of CRC patients. Following the successful development of anti-PD-1 for melanoma, renal cell carcinoma, and non-small cell lung cancer, several clinical trials have been conducted on monoclonal antibodies (MAbs) against PD-1 in CRC. There is a growing body of literature that recognizes the importance of anti-PD-1 therapy for MSI (Microsatellite instability) tumors among CRC subtypes. We present a comprehensive knowledge of immune therapy through PD-1/PD-L1 blockade that argues how efficient the process is, in colon cancer carcinoma. In this review, we discuss the responsiveness of immunotherapy on PD-1/PD-L1 blockade and various tactics for overcoming weak responses to these checkpoint inhibitors in CRC. More research using controlled trials is required to enable new discoveries to provide continued success with immune-based therapies and grounds for optimism about the future of CRC patients.

摘要

结直肠癌(CRC)作为癌症相关死亡的主要原因,在全球范围内一直备受关注,并且已经做出了许多尝试来提高 CRC 患者的总体生存率。免疫反应一直是癌症治疗和抗肿瘤免疫等广泛领域非常感兴趣的问题,通过检查点抑制剂,特别是抗 PD-1/PD-L1 相互作用,是治疗 CRC 患者的新研究方向。在抗 PD-1 在黑色素瘤、肾细胞癌和非小细胞肺癌方面取得成功开发后,已经在 CRC 中进行了多项针对 PD-1 的单克隆抗体(MAb)的临床试验。越来越多的文献认识到抗 PD-1 治疗 CRC 亚类中 MSI(微卫星不稳定性)肿瘤的重要性。我们全面了解了通过 PD-1/PD-L1 阻断的免疫治疗,论证了该过程在结肠癌中的效率如何。在这篇综述中,我们讨论了免疫疗法对 PD-1/PD-L1 阻断的反应性,以及克服 CRC 中这些检查点抑制剂反应较弱的各种策略。需要更多的对照试验研究来提供新的发现,以继续免疫治疗的成功,并为 CRC 患者的未来带来乐观的理由。

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