为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Current status and challenges of immune checkpoint inhibitors in liver cancer: from monotherapy to combination strategies.
Current status and challenges of immune checkpoint inhibitors in liver cancer: from monotherapy to combination strategies.
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肝细胞癌(HCC)预后极差。免疫检查点抑制剂(ICIs)的出现从根本上改变了HCC的治疗格局。然而,由于单药治疗缓解率有限且耐药机制复杂,临床实践的核心已转向以ICI为基础的联合策略。本文系统综述了这一范式转变背后的生物学基础——主要是免疫微环境——及临床证据,包括单药治疗的局限性和联合方案的优化,以及实现精准医学所面临的挑战(如疗效预测和耐药)。最后指出,未来的突破依赖于多组学指导的个体化方案、工程化免疫细胞技术和基于AI的预测模型的整合应用。总之,推动HCC免疫治疗从广谱联合策略向个体化精准联合迈进,是解决当前局限、提高治疗获益的一个有前景的方向。
Hepatocellular carcinoma (HCC) has an extremely poor prognosis. The emergence of immune checkpoint inhibitors (ICIs) has fundamentally transformed the therapeutic landscape for HCC.
However, due to the limited response rate and complex resistance mechanisms of monotherapy, the core of clinical practice has shifted towards ICI-based combination strategies. This article systematically reviews the biological basis-primarily the immune microenvironment-and clinical evidence, including the limitations of monotherapy and the optimization of combination regimens, underlying this paradigm shift, as well as the challenges in achieving precision medicine (such as efficacy prediction and resistance).
Finally, it points out that future breakthroughs rely on the integrated application of multi-omics-guided personalized regimens, engineered immune cell technologies, and AI-based predictive models. In summary, advancing HCC immunotherapy from broad combination strategies toward individualized precision combinations represents a promising direction for addressing current limitations and improving therapeutic benefit.
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