Fu Yan, Zeng Chu Hui, An Chao, Liu Yue, Shin Ji Hoon, Li Xiao
Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Cancers (Basel). 2023 Feb 19;15(4):1324. doi: 10.3390/cancers15041324.
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.
由于大多数肝细胞癌（HCC）患者在中晚期才被诊断出来，不再适合进行根治性治疗，因此HCC的总体生存率仍然不尽人意。局部区域介入治疗（LITs）和基于免疫检查点抑制剂（ICI）的免疫疗法致力于治疗HCC，但它们单独应用的疗效有限。因此，本综述的目的是探讨细胞因子的生物学作用及其在LITs与基于ICI的免疫疗法联合治疗中的治疗潜力。LITs的两种常见技术是消融疗法和经动脉疗法。LITs是否彻底在很大程度上会影响抗肿瘤免疫反应和肿瘤进展。详细讨论了诱导对LITs产生局部和全身反应的细胞因子，包括干扰素、白细胞介素、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及其作用。此外，还介绍了可作为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，肿瘤内不完全的LITs与特定细胞因子相结合，被认为可有效提高治疗效果并减少治疗引起的irAEs，为治疗无法切除的HCC带来了新希望。
