Tabrizian Parissa, Marino Rebecca, Chow Pierce K H
Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, USA.
Department of Hepato-pancreato-Biliary and Transplant Surgery, National Cancer Center Singapore and Singapore General Hospital, Singapore.
JHEP Rep. 2024 Aug 6;6(11):101181. doi: 10.1016/j.jhepr.2024.101181. eCollection 2024 Nov.
Immune checkpoint inhibitors (ICIs) have revolutionised the treatment landscape for advanced hepatocellular carcinoma (HCC). The combination of atezolizumab and bevacizumab has demonstrated efficacy, establishing a new standard of care for advanced HCC. Neoadjuvant studies have shown promising results with high response rates, increasing research into ICIs' role. In the peri-operative setting, in addition to adjuvant and neo-adjuvant therapies, strategies for "downstaging" and "bridging" patients to liver transplantation (LT) are being investigated, broadening the eligible candidate pool. Furthermore, therapeutic advances have reshaped conversion strategies for hepatic resection, with emerging evidence indicating a role for adjuvant immunotherapy in patients at high risk of postoperative recurrence. In LT, concerns have arisen over the potential conflict between immunosuppression needs and the immune-enhancing effects of ICIs, with reports of severe rejection. However, liver-specific factors may lessen rejection risks, prompting exploration into the safety of pre-transplant ICI administration. Moreover, ongoing trials must prioritise patient selection and vigilant management protocols. Despite the remarkable progress in immunotherapy, the intricate molecular interactions within the tumour microenvironment and their implications on oncogenic pathways remain incompletely understood. This highlights the need for specialised expertise to effectively integrate immunotherapy into the surgical management of HCC. Key challenges include ensuring safety, optimising oncological outcomes, managing the risk of graft rejection in transplant recipients, and refining patient selection criteria. In this review, we aim to provide a comprehensive overview of the evolving role of immunotherapy in the surgical management of HCC, discussing the rationale for its application in both pre- and post-surgical contexts, leveraging current clinical experience, identifying potential limitations, and envisioning future applications. By integrating existing knowledge and highlighting areas for further investigation, this review seeks to inform clinical practice and guide future research endeavours.
免疫检查点抑制剂（ICIs）彻底改变了晚期肝细胞癌（HCC）的治疗格局。阿替利珠单抗和贝伐单抗的联合使用已显示出疗效，为晚期HCC确立了新的治疗标准。新辅助研究显示出有前景的结果，反应率很高，这增加了对ICIs作用的研究。在围手术期，除了辅助和新辅助治疗外，正在研究将患者“降期”和“桥接”至肝移植（LT）的策略，从而扩大了符合条件的候选者群体。此外，治疗进展重塑了肝切除的转化策略，新出现的证据表明辅助免疫疗法在术后复发高风险患者中发挥作用。在LT中，人们对免疫抑制需求与ICIs的免疫增强作用之间的潜在冲突产生了担忧，有严重排斥反应的报告。然而，肝脏特异性因素可能会降低排斥风险，促使人们探索移植前ICI给药的安全性。此外，正在进行的试验必须优先考虑患者选择和警惕的管理方案。尽管免疫疗法取得了显著进展，但肿瘤微环境内复杂的分子相互作用及其对致癌途径的影响仍未完全了解。这凸显了需要专业知识才能有效地将免疫疗法纳入HCC的手术管理中。关键挑战包括确保安全性、优化肿瘤学结果、管理移植受者的移植物排斥风险以及完善患者选择标准。在本综述中，我们旨在全面概述免疫疗法在HCC手术管理中不断演变的作用，讨论其在手术前和手术后应用的原理，利用当前的临床经验，识别潜在局限性，并设想未来的应用。通过整合现有知识并突出需要进一步研究的领域，本综述旨在为临床实践提供信息并指导未来的研究工作。
