Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore.
Oncoimmunology. 2023 Jun 3;12(1):2214478. doi: 10.1080/2162402X.2023.2214478. eCollection 2023.
The use of immune checkpoint inhibitors (ICIs) targeting PD-L1/PD-1 and CTLA-4 has transformed the oncology practice of hepatocellular carcinoma. However, only 25-30% of the patients with advanced HCC treated with atezolizumab-bevacizumab or tremelimumab-durvalumab (STRIDE) respond initially, and mechanistic biomarkers and novel treatment strategies are urgently needed for patients who present with or acquire resistance to first-line ICI-based therapies. The recent approval of the STRIDE regimen has also engendered new questions, such as patient selection factors (e.g. portal hypertension and history of variceal bleed) and biomarkers, and the optimal combination and sequencing of ICI-based regimens. Triumphs in the setting of advanced HCC have also galvanized considerable interest in the broader application of ICIs to early- and intermediate-stage diseases, including clinical combination of ICIs with locoregional therapies. Among these clinical contexts, the role of ICIs in liver transplantation - which is a potentially curative strategy unique to HCC management - as a bridge to liver transplant in potential candidates or in the setting of post-transplant recurrence, warrants investigation in view of the notable theoretical risk of allograft rejection. In this review, we summarize and chart the landscape of seminal immuno-oncology trials in HCC and envision future clinical developments.
免疫检查点抑制剂（ICIs）靶向 PD-L1/PD-1 和 CTLA-4 的应用改变了肝细胞癌的肿瘤学实践。然而，只有 25-30%的晚期 HCC 患者对阿替利珠单抗-贝伐珠单抗或替西木单抗-度伐利尤单抗（STRIDE）治疗最初有反应，对于出现或对一线 ICI 治疗产生耐药的患者，需要有机制生物标志物和新的治疗策略。STRIDE 方案的最近批准也引发了新的问题，例如患者选择因素（例如门静脉高压和静脉曲张出血史）和生物标志物，以及基于 ICI 的方案的最佳组合和序贯。晚期 HCC 中的成功也激发了人们对将 ICI 更广泛地应用于早期和中期疾病的极大兴趣，包括将 ICI 与局部区域治疗联合应用于临床。在这些临床情况下，鉴于同种异体移植排斥的显著理论风险，ICI 在肝移植中的作用——这是 HCC 管理中一种独特的潜在治愈策略——作为潜在候选者的肝移植桥接或移植后复发的情况下，值得研究。在这篇综述中，我们总结并描绘了 HCC 中开创性的免疫肿瘤学试验的全景，并展望了未来的临床发展。
