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胰腺癌的免疫疗法:障碍与突破

Immunotherapy for pancreatic cancer: Barriers and breakthroughs.

作者信息

Torphy Robert J, Zhu Yuwen, Schulick Richard D

机构信息

Department of Surgery University of Colorado Aurora Colorado USA.

出版信息

Ann Gastroenterol Surg. 2018 Jun 22;2(4):274-281. doi: 10.1002/ags3.12176. eCollection 2018 Jul.

Abstract

Immunotherapy is a rapidly growing field and represents a paradigm shift in the treatment of malignancies as it offers a new therapeutic approach beyond surgery, conventional chemotherapy, and radiation treatment. Targeting immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 and programmed death 1/programmed death ligand 1 has had immense clinical success resulting in sustained treatment response for a subset of patients with certain malignancies such as melanoma, non-small-cell lung cancer, urothelial carcinoma, squamous cell carcinoma of the head and neck, renal cell cancer, hepatocellular cancer, and metastatic colorectal cancer. Importantly, there has been limited success in the use of immunotherapy in the treatment of pancreatic cancer. Investigation into the complex tumor microenvironment of pancreatic cancer that is composed of immune cells, stromal cells, and extracellular matrix proteins has begun to shed light on important attributes of this microenvironment that act as barriers to the effective use of immunotherapy. In this review, we will discuss the progress that has been made in treating pancreatic cancer with immunotherapy, the barriers that have limited treatment success, and breakthroughs with combination treatments that hold promise for the future.

摘要

免疫疗法是一个快速发展的领域,代表了恶性肿瘤治疗的范式转变,因为它提供了一种超越手术、传统化疗和放射治疗的新治疗方法。靶向免疫检查点,如细胞毒性T淋巴细胞相关抗原4和程序性死亡蛋白1/程序性死亡配体1,已取得巨大的临床成功,使一部分患有某些恶性肿瘤(如黑色素瘤、非小细胞肺癌、尿路上皮癌、头颈部鳞状细胞癌、肾细胞癌、肝细胞癌和转移性结直肠癌)的患者获得持续的治疗反应。重要的是,免疫疗法在胰腺癌治疗中的应用取得的成功有限。对由免疫细胞、基质细胞和细胞外基质蛋白组成的胰腺癌复杂肿瘤微环境的研究,已开始揭示该微环境中作为免疫疗法有效应用障碍的重要特征。在这篇综述中,我们将讨论免疫疗法治疗胰腺癌取得的进展、限制治疗成功的障碍以及有望在未来取得突破的联合治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dc0/6036358/c017920d11e7/AGS3-2-274-g001.jpg

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