Hepatocellular carcinoma (HCC) is estimated to be the fourth leading cause of cancer-related deaths globally, and its overall prognosis is dismal because most cases are diagnosed at a late stage and are unamenable to curative treatment. The emergence of immune checkpoint inhibitors (ICIs) has dramatically improved the therapeutic efficacy for advanced hepatocellular carcinoma; however, their response rates remain unsatisfactory, partly because >50% of HCC exhibit an ICI-nonresponsive tumor microenvironment characterized by a paucity of cytotoxic T cells (immune-cold), as well as difficulty in their infiltration into tumor sites (immune excluded). To overcome this limitation, combination therapies with locoregional therapies, including ablation, transarterial embolization, and radiotherapy, which are usually used for early stage HCCs, have been actively explored to enhance ICI efficacy by promoting the release of tumor-associated antigens and cytokines, and eventually accelerating the so-called cancer–immunity cycle. Various combination therapies have been investigated in early- to late-phase clinical trials, and some have shown promising results. This comprehensive article provides an overview of the immune landscape for HCC to understand ICI efficacy and its limitations and, subsequently, reviews the status of combinatorial therapies of ICIs with locoregional therapy for HCC.
肝细胞癌（HCC）是全球癌症相关死亡的第四大主要原因，其总体预后较差，因为大多数病例在晚期才被诊断，且无法接受根治性治疗。免疫检查点抑制剂（ICIs）的出现显著改善了晚期肝细胞癌的治疗效果；然而，其应答率仍不理想，部分原因是超过50%的肝细胞癌呈现出对ICI无应答的肿瘤微环境特征，表现为细胞毒性T细胞缺乏（免疫冷型）以及这些细胞难以浸润至肿瘤部位（免疫排斥型）。为克服这一局限，研究者正积极探索将免疫检查点抑制剂与局部区域疗法（包括消融术、经动脉栓塞术和放射治疗等通常用于早期肝细胞癌的手段）联合应用，通过促进肿瘤相关抗原和细胞因子的释放，最终加速所谓的癌症-免疫循环，从而增强免疫检查点抑制剂的疗效。目前已有多种联合疗法在早期至晚期临床试验中得到研究，其中部分已显示出令人鼓舞的结果。本文全面概述了肝细胞癌的免疫景观，以深入理解免疫检查点抑制剂的疗效及其局限性，并系统评述了免疫检查点抑制剂与局部区域疗法联合治疗肝细胞癌的研究现状。
肿瘤(癌症)患者之家