Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, and, with only 15–20% of HCC patients being suitable for potentially curative treatments, the vast majority of patients with HCC ultimately require systemic therapy. For decades, the choice of effective systemic therapy for HCC remained sparse. In recent years, after the combination of atezolizumab and bevacizumab demonstrated superior overall survival over the first-line standard, sorafenib, there has been a major therapeutic paradigm shift to immunotherapy-based regimens for HCC. While representing a great leap forward for the treatment of this cancer, the reality is that less than one-third of patients achieve an objective response to immune checkpoint inhibitor-based therapy, so there remains a significant clinical need for further therapeutic optimization. In this review, we provide an overview of the current landscape of immunotherapy for unresectable HCC and delve into the tumor intrinsic and extrinsic mechanisms of resistance to established immunotherapies with a focus on novel therapeutic targets with strong translational potential. Following this, we spotlight emerging immunotherapy approaches and notable clinical trials aiming to optimize immunotherapy efficacy in HCC that include novel immune checkpoint inhibitors, tumor microenvironment modulators, targeted delivery systems, and locoregional interventions.
肝细胞癌是全球癌症相关死亡的主要原因，由于仅有15%-20%的患者适合接受潜在根治性治疗，绝大多数患者最终需要全身性治疗。数十年来，肝细胞癌有效全身治疗方案的选择极为有限。近年来，随着阿特珠单抗联合贝伐珠单抗在总生存期方面显示出优于一线标准治疗药物索拉非尼的疗效，肝细胞癌治疗模式已发生重大转变，进入以免疫治疗为基础的方案时代。尽管这标志着该癌症治疗领域的重大进步，但现实情况是仅有不到三分之一的患者对基于免疫检查点抑制剂的治疗产生客观应答，因此临床上仍需进一步优化治疗方案。本综述概述了当前不可切除肝细胞癌免疫治疗的发展现状，深入探讨了已确立免疫疗法的肿瘤内在与外在耐药机制，重点关注具有强大转化潜力的新型治疗靶点。在此基础上，我们聚焦于新兴免疫治疗策略及旨在优化肝细胞癌免疫疗效的重要临床试验，包括新型免疫检查点抑制剂、肿瘤微环境调节剂、靶向递送系统以及局部介入治疗。
肿瘤(癌症)患者之家