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免疫检查点抑制剂在肝细胞癌中的新作用。

Emerging role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma.

作者信息

Longo Vito, Brunetti Oronzo, Gnoni Antonio, Licchetta Antonella, Delcuratolo Sabina, Memeo Riccardo, Solimando Antonio Giovanni, Argentiero Antonella

机构信息

Medical Thoracic Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II" of Bari, 70124 Bari, Italy.

Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II" of Bari, 70124 Bari, Italy.

出版信息

Medicina (Kaunas). 2019 Oct 17;55(10):698. doi: 10.3390/medicina55100698.


DOI:10.3390/medicina55100698
PMID:31627433
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6843273/
Abstract

Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70-80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib had been the standardcare for almost a decade until 2018 when the Food and Drug Administration approved an alternative first-line agent namely lenvatinib. Cabozantinib, regorafenib, and ramucirumab also displayed promising results in second line settings. FOLFOX4, however, results inan alternative first-line treatment for the Chineseclinical oncology guidelines. Moreover,nivolumab and pembrolizumab,two therapeutics against the Programmed death (PD)-ligand 1 (PD-L1)/PD1 axis have been recently approvedfor subsequent-line therapy. However, similar to other solid tumors, the response rate of single agent targeting PD-L1/PD1 axis is low. Therefore, a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors (ICIs), the addition of ICIs after resection or during loco-regional therapy, ICIs in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with a careful assessmentof new ICIs-based combinatory approaches.

摘要

肝细胞癌是最常见的原发性肝癌,也是全球癌症死亡的第四大主要原因。共有70%-80%的患者在晚期被诊断出来,预后不佳。在2018年美国食品药品监督管理局批准另一种一线药物乐伐替尼之前,索拉非尼一直是近十年的标准治疗药物。卡博替尼、瑞戈非尼和雷莫西尤单抗在二线治疗中也显示出了有前景的结果。然而,FOLFOX4是中国临床肿瘤学会指南中的一种一线替代治疗方案。此外,纳武利尤单抗和帕博利珠单抗这两种针对程序性死亡(PD)-配体1(PD-L1)/PD1轴的治疗药物最近已被批准用于后续治疗。然而,与其他实体瘤类似,单药靶向PD-L1/PD1轴的缓解率较低。因此,许多联合治疗方法正在研究中,包括不同免疫检查点抑制剂(ICI)的联合、切除术后或局部区域治疗期间添加ICI、ICI联合激酶抑制剂、抗血管生成治疗药物等。本综述重点关注ICI在肝细胞癌中的应用,并仔细评估基于ICI的新联合治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3c/6843273/a17e0badfbcc/medicina-55-00698-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3c/6843273/a17e0badfbcc/medicina-55-00698-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3c/6843273/a17e0badfbcc/medicina-55-00698-g001.jpg

相似文献

[1]
Emerging role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma.

Medicina (Kaunas). 2019-10-17

[2]
Molecular targeted and immune checkpoint therapy for advanced hepatocellular carcinoma.

J Exp Clin Cancer Res. 2019-11-4

[3]
Pharmacogenetics of the systemic treatment in advanced hepatocellular carcinoma.

World J Gastroenterol. 2019-8-7

[4]
Molecular therapies for HCC: Looking outside the box.

J Hepatol. 2020-2

[5]
Review article: systemic treatment of hepatocellular carcinoma.

Aliment Pharmacol Ther. 2018-7-23

[6]
Lenvatinib for hepatocellular carcinoma: From preclinical mechanisms to anti-cancer therapy.

Biochim Biophys Acta Rev Cancer. 2020-7-10

[7]
Drug Treatment for Advanced Hepatocellular Carcinoma: First-Line and Beyond.

Curr Oncol. 2022-8-4

[8]
Immunomodulatory Effects of Current Targeted Therapies on Hepatocellular Carcinoma: Implication for the Future of Immunotherapy.

Semin Liver Dis. 2018-10-24

[9]
Immunomodulatory activity of lenvatinib contributes to antitumor activity in the Hepa1-6 hepatocellular carcinoma model.

Cancer Sci. 2018-11-16

[10]
Targeted therapy for hepatocellular carcinoma.

Signal Transduct Target Ther. 2020-8-11

引用本文的文献

[1]
Immunotherapy and liver transplantation for hepatocellular carcinoma: Current and future challenges.

World J Transplant. 2025-6-18

[2]
Apolipoprotein E: A Potential Prognostic and Diagnostic Biomarker for Hepatocellular Carcinoma.

J Hepatocell Carcinoma. 2025-2-17

[3]
Lenvatinib, sintilimab combined interventional treatment bevacizumab, sintilimab combined interventional treatment for intermediate-advanced unresectable hepatocellular carcinoma.

World J Gastroenterol. 2024-11-21

[4]
Fatty acid synthase inhibitor cerulenin hinders liver cancer stem cell properties through FASN/APP axis as novel therapeutic strategies.

J Lipid Res. 2024-11

[5]
Antibiotic Exposure Concurrently with Anti-PD1 Blockade Therapy Reduces Overall Survival in Patients with Child-Pugh Class A Advanced Hepatocellular Carcinoma.

Cancers (Basel). 2023-12-27

[6]
The worthy role of hepatic arterial infusion chemotherapy in combination with anti-programmed cell death protein 1 monoclonal antibody immunotherapy in advanced hepatocellular carcinoma.

Front Immunol. 2023

[7]
Potential Immunotherapy Targets for Liver-Directed Therapies, and the Current Scope of Immunotherapeutics for Liver-Related Malignancies.

Cancers (Basel). 2023-5-5

[8]
The Prognostic Significance of and Its Related Immune Infiltration in Liver Hepatocellular Carcinoma.

Int J Mol Sci. 2022-10-24

[9]
Association between germ-line HLA and immune-related adverse events.

Front Immunol. 2022

[10]
Dendritic-Cell-Vaccine-Based Immunotherapy for Hepatocellular Carcinoma: Clinical Trials and Recent Preclinical Studies.

Cancers (Basel). 2022-9-8

本文引用的文献

[1]
Predictive and Prognostic Factors in HCC Patients Treated with Sorafenib.

Medicina (Kaunas). 2019-10-21

[2]
Gene Expression Comparison between the Lymph Node-Positive and -Negative Reveals a Peculiar Immune Microenvironment Signature and a Theranostic Role for WNT Targeting in Pancreatic Ductal Adenocarcinoma: A Pilot Study.

Cancers (Basel). 2019-7-4

[3]
Strategies to Improve Cancer Immune Checkpoint Inhibitors Efficacy, Other Than Abscopal Effect: A Systematic Review.

Cancers (Basel). 2019-4-15

[4]
CAFs and TGF-β Signaling Activation by Mast Cells Contribute to Resistance to Gemcitabine/Nabpaclitaxel in Pancreatic Cancer.

Cancers (Basel). 2019-3-7

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Bone marrow endothelial cells sustain a tumor-specific CD8 T cell subset with suppressive function in myeloma patients.

Oncoimmunology. 2018-10-22

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Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.

CA Cancer J Clin. 2018-9-12

[7]
Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma.

N Engl J Med. 2018-7-5

[8]
Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial.

Lancet Oncol. 2018-6-3

[9]
Targeting VEGF/VEGFR to Modulate Antitumor Immunity.

Front Immunol. 2018-5-3

[10]
Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial.

Lancet. 2018-3-24

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