How Biology Guides the Combination of Locoregional Interventional Therapies and Immunotherapy for Hepatocellular Carcinoma: Cytokines and Their Roles.
How Biology Guides the Combination of Locoregional Interventional Therapies and Immunotherapy for Hepatocellular Carcinoma: Cytokines and Their Roles.
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生物学如何指导肝细胞癌局部介入治疗和免疫治疗的结合：细胞因子及其作用
作者：
不能切除的肝细胞癌是原发性肝癌的主要类型，对世界各地的医疗保健系统构成了挑战。以免疫检查点抑制物(ICI)为基础的免疫治疗已成为肝癌治疗的研究热点。然而，其与治疗相关的严重不良事件的高风险使得降低毒性和改善临床结果的有效组合策略成为迫切需要。虽然局部介入治疗被认为是通过促进肿瘤抗原和促炎细胞因子的释放来协同基于ICI的免疫治疗的有前途的策略，但目前的临床试验显示出有争议的结果。鉴于细胞因子在LITS和免疫联合治疗中的重要作用，本文就细胞因子在LITS联合ICI免疫治疗中的生物学作用及其治疗潜力作一综述。由于大多数肝细胞癌患者被诊断为中晚期，不再有资格接受根治性治疗，肝细胞癌的总体存活率仍然不令人满意。局部介入治疗(LITS)和基于免疫检查点抑制物(ICI)的免疫治疗主要用于治疗肝癌，但其单独应用的疗效有限。因此，本综述的目的是讨论细胞因子在LITS和ICI免疫联合治疗中的生物学作用及其治疗潜力。LITS的两种常见技术是消融和经动脉治疗。LITS的完整或不完全在很大程度上影响抗肿瘤免疫反应和肿瘤进展。详细讨论了诱导局部和全身反应的细胞因子，包括干扰素、白介素类、趋化因子、肿瘤坏死因子-α、转化生长因子-β、血管内皮生长因子和肝细胞生长因子，以及它们的作用。此外，还介绍了可用作治疗靶点以减少免疫相关不良事件(IrAEs)的特定细胞因子。总体而言，肿瘤中的不完全LITS结合特定的细胞因子被认为在提高治疗效果和减少治疗诱导的irAEs方面是有效的，并代表着治疗不能切除的肝癌的新希望。
Unresectable hepatocellular carcinoma (HCC) is the main type of primary liver cancer and poses a challenge to the healthcare system across the world. Immune checkpoint inhibitor (ICI)-based immunotherapy has become a recent focus of HCC treatment. However, its high risk of treatment-related severe adverse events makes effective combination strategies to lower toxicity and improve clinical outcomes an urgent need. Although locoregional interventional therapies are considered promising strategies to synergize ICI-based immunotherapies by promoting the release of tumor antigens and proinflammatory cytokines, current clinical trials show controversial results. Since cytokines play critical roles in the combination therapy of LITs and immunotherapy, this review aims to summarize the biological roles of cytokines and their therapeutic potentials in the LITs combined with ICI-based immunotherapies. As most patients with hepatocellular carcinoma (HCC) are diagnosed at the intermediate or advanced stage and are no longer eligible for curative treatment, the overall survival rate of HCC remains unsatisfactory. Locoregional interventional therapies (LITs), and immune checkpoint inhibitor (ICI)-based immunotherapy, focus on treating HCC, but the efficacy of their individual application is limited. Therefore, the purpose of this review was to discuss the biological roles of cytokines and their therapeutic potential in the combination therapy of LITs and ICI-based immunotherapy. The two common techniques of LITs are ablative and transarterial therapies. Whether LITs are complete or incomplete can largely affect the antitumor immune response and tumor progression. Cytokines that induce both local and systemic responses to LITs, including interferons, interleukins, chemokines, TNF-α, TGF-β, VEGF, and HGF, and their roles are discussed in detail. In addition, specific cytokines that can be used as therapeutic targets to reduce immune-related adverse events (irAEs) are introduced. Overall, incomplete LITs in a tumor, combined with specific cytokines, are thought to be effective at improving the therapeutic efficacy and reducing treatment-induced irAEs, and represent a new hope for managing unresectable HCC.
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影响因子：
7.3
作者：
Albakova Z;Mangasarova Y
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Mangasarova Y
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5
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25.7
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Finn, Richard S.
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3.1
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Dong, BW;Zhang, J;Yu, G
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Yu, G