Abstract:
Immune checkpoints (ICPs) can promote tumor growth and prevent immunity-induced cancer cell apoptosis. Fortunately, targeting ICPs, such as programmed cell death 1 (PD-1) or cytotoxic T lymphocyte associated protein 4 (CTLA-4), has achieved great success in the past few years and has gradually become an effective treatment for cancers, including hepatocellular carcinoma (HCC). However, many patients do not respond to ICP therapy due to acquired resistance and recurrence. Therefore, clarifying the specific mechanisms of ICP in the development of HCC is very important for enhancing the efficacy of anti-PD-1 and anti-CTLA-4 therapy. In particular, antigen presentation and interferon-γ (IFN-γ) signaling were reported to be involved in the development of resistance. In this review, we have explained the role and regulatory mechanisms of ICP therapy in HCC pathology. Moreover, we have also elaborated on combinations of ICP inhibitors and other treatments to enhance the antitumor effect. Collectively, recent advances in the pharmacological targeting of ICPs provide insights for the development of a novel alternative treatment for HCC.
摘要:
免疫检查点(ICPs)可以促进肿瘤生长并防止免疫诱导的癌细胞凋亡。幸运的是,针对ICP,如程序性细胞死亡1(PD-1)或细胞毒性T淋巴细胞相关蛋白4(CTLA-4),在过去的几年中取得了巨大的成功,并逐渐成为癌症的有效治疗方法,包括肝细胞癌(HCC)。然而,由于获得性耐药和复发,许多患者对ICP治疗无反应.因此,阐明ICP在HCC发展中的具体机制对于提高抗PD-1和抗CTLA-4治疗的疗效非常重要。特别是,据报道,抗原呈递和干扰素-γ(IFN-γ)信号参与耐药性的发展.在这次审查中,我们已经解释了ICP治疗在HCC病理中的作用和调节机制。此外,我们还详细阐述了ICP抑制剂和其他治疗方法的组合,以增强抗肿瘤效果。总的来说,ICPs的药理学靶向研究的最新进展为HCC的新型替代疗法的开发提供了见解。