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肝细胞癌和胆管癌免疫治疗的现状与未来

The present and the future of immunotherapy in hepatocellular carcinoma and biliary tract cancers.

作者信息

Cabibbo Giuseppe, Rimassa Lorenza, Lamarca Angela, Masi Gianluca, Daniele Bruno, Pinato David James, Casadei-Gardini Andrea

机构信息

Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Piazza delle Cliniche n 2, 90127 Palermo, Italy.

Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy; Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via A. Manzoni 56, 20089 Rozzano, Milan, Italy.

出版信息

Cancer Treat Rev. 2025 Jun;137:102955. doi: 10.1016/j.ctrv.2025.102955. Epub 2025 May 9.

Abstract

Hepatobiliary malignancies encompass a spectrum of invasive carcinomas arising in the liver [hepatocellular carcinoma (HCC), bile ducts [intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (EHC)] and the gallbladder. These malignancies represent a growing global health burden, with rising incidence and mortality rates and their overall prognosis remains poor because many patients present with advanced unresectable disease at diagnosis. In recent years, significant advancements in understanding HCC immunogenicity have reshaped the therapeutic scenario of advanced HCC with the immunotherapy revolutionizing the current HCC treatment landscape and patients' prognosis. Moreover, the addition of immunotherapy to chemotherapy has recently established a new standard of care first-line treatment for patients with biliary tract cancers (BTCs) who had historically few therapeutic options. Currently, immunotherapy and immune checkpoint inhibitor (ICI)-based regimens stand as a valuable and practice-changing options in both HCC and BTC management. The mounting recent evidence supporting immunotherapy's survival benefit demands clinicians to stay updated with a rapidly evolving treatment landscape as well as gain knowledge about patient selection, response rate compared with other systemic treatments and immune-mediated adverse events (imAEs) management. A panel of international Experts, comprising hepatologists and oncologists, gathered to explore the challenges in effectively integrating immunotherapy in routine clinical practice. The aim of this review is to present the Experts' insights to inform treatment choice in HCC and BTC with a special emphasis on the role of currently available ICI-based therapies in shifting treatment paradigms and potentially reversing the natural course of these two deadly malignancies.

摘要

肝胆恶性肿瘤包括一系列起源于肝脏的浸润性癌(肝细胞癌)、胆管(肝内胆管癌和肝外胆管癌)以及胆囊癌。这些恶性肿瘤在全球范围内造成的健康负担日益加重,发病率和死亡率不断上升,而且由于许多患者在诊断时已出现无法切除的晚期疾病,其总体预后仍然很差。近年来,在理解肝癌免疫原性方面取得的重大进展重塑了晚期肝癌的治疗格局,免疫疗法彻底改变了当前肝癌的治疗模式和患者的预后。此外,最近在化疗中加入免疫疗法,为历来治疗选择有限的胆管癌患者确立了一线治疗的新护理标准。目前,免疫疗法和基于免疫检查点抑制剂的治疗方案在肝癌和胆管癌的治疗中都是有价值且改变治疗模式的选择。最近越来越多的证据支持免疫疗法对生存有益,这就要求临床医生紧跟快速发展的治疗格局,了解患者选择、与其他全身治疗相比的缓解率以及免疫介导的不良事件管理等方面的知识。一组由肝病学家和肿瘤学家组成的国际专家齐聚一堂,探讨在常规临床实践中有效整合免疫疗法所面临的挑战。本综述的目的是介绍专家们的见解,为肝癌和胆管癌的治疗选择提供参考,特别强调目前可用的基于免疫检查点抑制剂的疗法在改变治疗模式以及可能逆转这两种致命恶性肿瘤自然病程方面的作用。

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