Background

Treatment of hepatocellular carcinoma (HCC) is challenging as most patients are diagnosed at advanced stage with underlying chronic liver conditions. Conventional systemic chemotherapy has failed in HCC, and the clinical efficacy of FDA-approved molecular targeted agents such as sorafenib and lenvatinib remains unsatisfactory.

Data sources

Literature search was conducted in PubMed for relevant articles published before January 2021. The search aimed to identify recent developments in immune-based treatment approaches for HCC. Information of clinical trials was obtained from https://clinicaltrials.gov/.

Results

Two immune checkpoint inhibitors (ICIs), nivolumab and pembrolizumab were approved as monotherapies, which has revolutionized HCC treatment. Besides, combination ICIs have also got accelerated FDA approval recently. Immune-based therapies have challenged targeted drugs owing to their safety, tolerability, and survival benefits. In addition to the significant success in ICIs, other immunotherapeutic strategies such as cancer vaccine, chimeric antigen receptor T-cells, natural killer cells, cytokines, and combination therapy, have also shown promising outcomes in clinical trials. Various diagnostic and prognostic biomarkers have been identified which can help in clinical decision making when starting treatment with ICIs.

Conclusions

Immunotherapy has emerged as one of the mainstream treatment modalities for advanced HCC in recent years. However, challenges such as low response rate and acquired resistance in previously respondent patients still exist. Further research is needed to understand the unique resistance mechanism to immunotherapy and to discover more predictive biomarkers to guide clinical decision making.

中文翻译：

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肝细胞癌免疫治疗的最新进展

背景

肝细胞癌 (HCC) 的治疗具有挑战性，因为大多数患者在晚期被诊断出患有潜在的慢性肝病。HCC 的常规全身化疗已失败，FDA 批准的分子靶向药物如索拉非尼和乐伐替尼的临床疗效仍不能令人满意。

数据源

在 PubMed 中对 2021 年 1 月之前发表的相关文章进行了文献搜索。搜索旨在确定基于免疫的 HCC 治疗方法的最新进展。临床试验信息来自 https://clinicaltrials.gov/。

结果

两种免疫检查点抑制剂 (ICI)，纳武单抗和派姆单抗被批准为单一疗法，彻底改变了 HCC 治疗。此外，组合ICI最近也获得了FDA的加速批准。基于免疫的疗法因其安全性、耐受性和生存益处而对靶向药物提出了挑战。除了在 ICI 中取得重大成功外，其他免疫治疗策略，如癌症疫苗、嵌合抗原受体 T 细胞、自然杀伤细胞、细胞因子和联合疗法，也在临床试验中显示出有希望的结果。已经确定了各种诊断和预后生物标志物，它们可以在开始 ICI 治疗时帮助临床决策。

结论

近年来，免疫疗法已成为晚期HCC的主流治疗方式之一。然而，先前反应患者的反应率低和获得性耐药等挑战仍然存在。需要进一步的研究来了解免疫治疗的独特耐药机制，并发现更多的预测性生物标志物来指导临床决策。