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肝细胞癌(HCC)抗 PD-1 单克隆抗体免疫治疗:一种快速演变的策略

英文原题:Hepatocellular carcinoma (HCC) immunotherapy by anti-PD-1 monoclonal antibodies: A rapidly evolving strategy.

查看英文原题

Hepatocellular carcinoma (HCC) immunotherapy by anti-PD-1 monoclonal antibodies: A rapidly evolving strategy.

PubMed 2023/04/20(内容时间) Pathol Res Pract Q1 · IF 3.7(JCR 2025)

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中文摘要

肝细胞癌(HCC)是全球最致命的癌症之一,复发率高。70-80%的患者出现症状延迟,导致诊断时已处于晚期,通常与慢性肝病相关。程序性细胞死亡蛋白1(PD-1)阻断疗法最近已成为包括HCC在内的多种晚期恶性肿瘤临床管理中有前景的治疗选择,这是由于耗竭的TIL(肿瘤浸润淋巴细胞)被激活以及T细胞功能改善的结果。

然而,许多HCC患者对PD-1阻断疗法无应答,且免疫相关不良事件(irAEs)的多样性限制了其临床应用。因此,许多有效的联合策略正在发展,包括与抗PD-1抗体联合以及其他从化疗到靶向治疗的治疗方法,以改善晚期HCC患者的治疗结果并激发协同抗肿瘤效应。不幸的是,联合治疗可能比单药治疗有更多副作用。尽管如此,识别合适的预测性生物标志物可以通过区分对PD-1抑制剂单药或联合策略应答最佳的患者,有助于管理潜在的免疫相关不良事件。在本综述中,我们总结了PD-1阻断疗法对晚期HCC患者的治疗潜力。

此外,将简要介绍影响患者对抗PD-1抗体应答的关键预测性生物标志物。

展开英文摘要原文

Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world, with a high relapse rate. Delayed symptom onset observed in 70-80% of patients leads to diagnosis in advanced stages commonly associated with chronic liver disease. Programmed cell death protein 1 (PD-1) blockade therapy has recently emerged as a promising therapeutic option in the clinical management of several advanced malignancies, including HCC, due to the activation of exhausted tumor-infiltrating lymphocytes and improved outcomes of T-cell function.

However, many people with HCC do not respond to PD-1 blockade therapy, and the diversity of immune-related adverse events (irAEs) restricts their clinical utility.

Therefore, numerous effective combinatory strategies, including combinations with anti-PD-1 antibodies and other therapeutic methods ranging from chemotherapy to targeted therapies, are evolving to improve therapeutic outcomes and evoke synergistic anti-tumor impressions in patients with advanced HCC. Unfortunately, combined therapy may have more side effects than single-agent treatment.

Nonetheless, identifying appropriate predictive biomarkers can aid in managing potential immune-related adverse events by distinguishing patients who respond best to PD-1 inhibitors as single agents or in combination strategies. In the present review, we summarize the therapeutic potential of PD-1 blockade therapy for advanced HCC patients. Besides, a glimpse of the pivotal predictive biomarkers influencing a patient's response to anti-PD-1 antibodies will be provided.

论文信息

作者
Nikoo M、Hassan ZF、Mardasi M、Rostamnezhad E、Roozbahani F、Rahimi S、Mohammadi J
第一作者单位
Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.Iran
通讯作者单位
Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran. Electronic address: javad.mohammadi@ut.ac.ir.Iran
文献类型
综述
期刊
Pathology, research and practice2023 Jul
原文标识
PubMed 37207558 · DOI 10.1016/j.prp.2023.154473