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肝细胞癌靶向免疫联合治疗的现状与展望。

The current status and future of targeted-immune combination for hepatocellular carcinoma.

机构信息

Clinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.

Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.

出版信息

Front Immunol. 2024 Aug 5;15:1418965. doi: 10.3389/fimmu.2024.1418965. eCollection 2024.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers and the third leading cause of death worldwide. surgery, transarterial chemoembolization (TACE), systemic therapy, local ablation therapy, radiotherapy, and targeted drug therapy with agents such as sorafenib. However, the tumor microenvironment of liver cancer has a strong immunosuppressive effect. Therefore, new treatments for liver cancer are still necessary. Immune checkpoint molecules, such as programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen-4 (CTLA-4), along with high levels of immunosuppressive cytokines, induce T cell inhibition and are key mechanisms of immune escape in HCC. Recently, immunotherapy based on immune checkpoint inhibitors (ICIs) as monotherapy or in combination with tyrosine kinase inhibitors, anti-angiogenesis drugs, chemotherapy agents, and topical therapies has offered great promise in the treatment of liver cancer. In this review, we discuss the latest advances in ICIs combined with targeted drugs (targeted-immune combination) and other targeted-immune combination regimens for the treatment of patients with advanced HCC (aHCC) or unresectable HCC (uHCC), and provide an outlook on future prospects. The literature reviewed spans the last five years and includes studies identified using keywords such as "hepatocellular carcinoma," "immune checkpoint inhibitors," "targeted therapy," "combination therapy," and "immunotherapy".

摘要

肝细胞癌(HCC)是最常见的癌症之一,也是全球第三大致死原因。目前的治疗方法包括手术、经动脉化疗栓塞(TACE)、系统治疗、局部消融治疗、放疗以及索拉非尼等靶向药物治疗。然而,肝癌的肿瘤微环境具有很强的免疫抑制作用。因此,仍然需要新的肝癌治疗方法。免疫检查点分子,如程序性死亡受体-1(PD-1)、程序性死亡配体 1(PD-L1)和细胞毒性 T 淋巴细胞相关抗原 4(CTLA-4),以及高水平的免疫抑制细胞因子,诱导 T 细胞抑制,是 HCC 免疫逃逸的关键机制。最近,基于免疫检查点抑制剂(ICIs)的免疫疗法作为单一疗法或与酪氨酸激酶抑制剂、抗血管生成药物、化疗药物和局部治疗联合应用,为肝癌的治疗带来了很大的希望。在这篇综述中,我们讨论了 ICIs 联合靶向药物(靶向免疫联合)和其他靶向免疫联合方案治疗晚期 HCC(aHCC)或不可切除 HCC(uHCC)患者的最新进展,并对未来前景进行了展望。综述的文献跨度为过去五年,包括使用“肝细胞癌”、“免疫检查点抑制剂”、“靶向治疗”、“联合治疗”和“免疫治疗”等关键词识别的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0785/11330771/23bf058f2acd/fimmu-15-1418965-g001.jpg

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