Brackenier Cedric, Kinget Lisa, Cappuyns Sarah, Verslype Chris, Beuselinck Benoit, Dekervel Jeroen
Department of Gastro-Enterology and Hepatology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
Cancers (Basel). 2023 Jan 5;15(2):348. doi: 10.3390/cancers15020348.
Tyrosine kinase inhibitors (TKIs) with antiangiogenic properties, such as sorafenib, have been the standard choice to systemically treat hepatocellular carcinoma for over a decade. More recently, encouraging results were obtained using immune checkpoint inhibitors, although head-to-head comparisons with sorafenib in phase 3 trials could not demonstrate superiority in terms of overall survival. The IMbrave150 was a breakthrough study that resulted in atezolizumab/bevacizumab, a combination of an antiangiogenic and an immune checkpoint inhibitor, as a new standard of care for advanced HCC. This review discusses the mode of action, clinical efficacy, and biomarker research for both drug classes and for the combination therapy. Moreover, the synergy between atezolizumab and bevacizumab is highlighted, unraveling pathophysiological mechanisms underlying an enhanced anticancer immunity by changing the immunosuppressed to a more immunoreactive tumor microenvironment (TME). This is achieved by upregulation of antigen presentation, upregulation of T-cell proliferation, trafficking and infiltration, impairing recruitment, and proliferation of immunosuppressive cells in the TME. However, more insights are needed to identify biomarkers of response that may improve patient selection and outcome.
具有抗血管生成特性的酪氨酸激酶抑制剂（TKIs），如索拉非尼，在过去十多年里一直是系统性治疗肝细胞癌的标准选择。最近，使用免疫检查点抑制剂取得了令人鼓舞的结果，尽管在3期试验中与索拉非尼进行的头对头比较未能在总生存期方面证明其优越性。IMbrave150研究是一项突破性研究，其结果是阿替利珠单抗/贝伐单抗（一种抗血管生成药物与一种免疫检查点抑制剂的联合用药）成为晚期肝癌的新护理标准。本综述讨论了这两类药物以及联合疗法的作用方式、临床疗效和生物标志物研究。此外，还强调了阿替利珠单抗和贝伐单抗之间的协同作用，通过将免疫抑制的肿瘤微环境（TME）转变为更具免疫反应性的TME，揭示了增强抗癌免疫力的病理生理机制。这是通过上调抗原呈递、上调T细胞增殖、运输和浸润、损害免疫抑制细胞在TME中的募集和增殖来实现的。然而，需要更多的见解来确定可能改善患者选择和预后的反应生物标志物。
