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?
英文原题:Immunotherapy targeting liver cancer tumor-initiating cells: challenges, mechanisms, and emerging therapeutic horizons.
Immunotherapy targeting liver cancer tumor-initiating cells: challenges, mechanisms, and emerging therapeutic horizons.
尽管现有治疗方法已显示出前景,但仍需进一步研究以阐明TICs的起源、建立准确的诊断方法并克服耐药性,最终提高肝癌治疗效果并改善患者预后。
肝癌是全球主要的健康负担,其中肝细胞癌(HCC)是最常见的类型。肝癌肿瘤起始细胞(TICs)是导致复发、转移和治疗耐药的原因,从而带来了严峻的治疗挑战。本综述全面总结了肝癌TICs的生物学特征,包括其潜在的细胞起源、诊断难点、关键信号通路以及与肿瘤免疫微环境的复杂相互作用。特别强调了免疫治疗策略,这些策略已显示出显著进展,但仍受限于TIC诱导的免疫耐药。本综述讨论了当前的方法,如免疫检查点抑制剂(ICIs)、过继性细胞疗法和肿瘤疫苗,以及将免疫治疗与化疗、靶向治疗和局部区域干预相结合的联合策略。此外,正在探索新兴策略,包括基因编辑、靶向酪氨酸激酶抑制和基于人工智能的肿瘤预测,以评估其提高治疗疗效的潜力。本综述的意义在于强调克服TICs带来的挑战以提高肝癌治疗疗效的重要性。总之,尽管现有治疗方法已显示出前景,但仍需进一步研究以阐明TICs的起源、建立准确的诊断方法并克服耐药性,最终提高肝癌治疗的疗效并改善患者预后。
Liver cancer is a major global health burden, with hepatocellular carcinoma (HCC) being the most common type. Liver cancer tumor-initiating cells (TICs) are responsible for recurrence, metastasis, and therapeutic resistance, thereby presenting formidable treatment challenges. This review provides a comprehensive summary of the biological features of liver cancer TICs, including their potential cellular origins, diagnostic difficulties, key signaling pathways, and complex interactions with the tumor immune microenvironment. Special emphasis is placed on immunotherapeutic strategies, which have shown notable progress but remain limited by TIC-induced immune resistance. The review discusses current approaches such as immune checkpoint inhibitors (ICIs), adoptive cell therapies, and tumor vaccines, as well as combination strategies integrating immunotherapy with chemotherapy, targeted therapy, and locoregional interventions. Furthermore, emerging strategies including gene editing, targeted tyrosine kinase inhibition, and artificial intelligence-based tumor prediction are being explored for their potential to improve therapeutic efficacy. The significance of this review lies in highlighting the importance of surmounting the challenges presented by TICs to boost the efficacy of liver cancer treatment. In conclusion, although existing treatment approaches have demonstrated promise, further research is warranted to elucidate the origins of TICs, establish accurate diagnostic methods, and overcome resistance, ultimately enhancing the efficacy of liver cancer treatment and improving patient outcomes.
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