Immunotherapy for pancreatic ductal adenocarcinoma: Challenges and opportunities
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摘要: 胰腺导管腺癌(PDAC)是胰腺癌中最常见的一种恶性肿瘤类型,且极易发生微转移。尽管近年来恶性肿瘤的免疫治疗取得重大进步,以程序性细胞死亡蛋白-1/程序性死亡配体-1抗体为代表的免疫检查点阻断,彻底改变了非小细胞肺癌、黑色素瘤、尿路上皮癌和肾癌等的临床诊疗。然而,由于PDAC的低免疫原性和独特的肿瘤微环境(TME),该免疫治疗方案在PDAC中并不尽如人意,PDAC的5年生存率在所有恶性肿瘤中仍为最差。随着对PDAC-TME的研究发展和理解的深入,深度解析免疫系统、肿瘤细胞和基质信号之间高度复杂的相互作用网络,将有助于开发针对PDAC免疫疗法的合理组合。通过阐述PDAC-TME的免疫独特性,探讨PDAC的潜在治疗机会以及相关临床研究进展。Abstract: Pancreatic ductal adenocarcinoma ( PDAC) is the most common type of pancreatic cancer, and its micrometastases are commonly seen in clinical practice. Although great progress has been made in immunotherapy for malignancies in recent years, immune checkpoint blockade focusing on programmed cell death protein 1 ( PD-1) /programmed death-ligand 1 ( PD-L1) has changed the clinical diagnosis and treatment of non-small cell lung cancer, melanoma, urothelial carcinoma, and renal carcinoma. However, the clinical effect of immunotherapy in PDAC is limited by the low immunogenicity and unique tumor microenvironment ( TME) of PDAC. With the research advances in PDAC-TME, an in-depth analysis of the highly complex interaction network between immune system, tumor cell, and matrix signal may help to develop a rational combination of immunotherapies for PDAC. By elaborating on the unique immunological features of PDAC-TME, this article reviews the potential treatment opportunities for PDAC and the advances in clinical research.
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