Bloom Matthew, Podder Sourav, Dang Hien, Lin Daniel
Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA.
Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA.
Int J Mol Sci. 2025 Feb 24;26(5):1936. doi: 10.3390/ijms26051936.
Over the past several years, the therapeutic landscape for patients with advanced, unresectable, or metastatic hepatocellular carcinoma has been transformed by the incorporation of checkpoint inhibitor immunotherapy into the treatment paradigm. Frontline systemic treatment options have expanded beyond anti-angiogenic tyrosine kinase inhibitors, such as sorafenib, to a combination of immunotherapy approaches, including atezolizumab plus bevacizumab and durvalumab plus tremelimumab, both of which have demonstrated superior response and survival to sorafenib. Additionally, combination treatments with checkpoint inhibitors and tyrosine kinase inhibitors have been investigated with variable success. In this review, we discuss these advances in systemic treatment with immunotherapy, with a focus on understanding both the underlying biology and mechanism of these strategies and their efficacy outcomes in clinical trials. We also review challenges in identifying predictive biomarkers of treatments and discuss future directions with novel immunotherapy targets.
在过去几年中，通过将检查点抑制剂免疫疗法纳入治疗模式，晚期、不可切除或转移性肝细胞癌患者的治疗格局发生了转变。一线全身治疗选择已从抗血管生成酪氨酸激酶抑制剂（如索拉非尼）扩展到免疫疗法的联合应用，包括阿替利珠单抗加贝伐单抗以及度伐利尤单抗加曲美木单抗，这两种联合疗法均已证明在疗效和生存期方面优于索拉非尼。此外，检查点抑制剂与酪氨酸激酶抑制剂的联合治疗也已进行了研究，取得了不同程度的成功。在本综述中，我们讨论免疫疗法在全身治疗方面的这些进展，重点是了解这些策略的潜在生物学特性和机制及其在临床试验中的疗效结果。我们还回顾了确定治疗预测生物标志物方面的挑战，并讨论了新型免疫疗法靶点的未来发展方向。
