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:Harnessing Dendritic Cell Function in Hepatocellular Carcinoma: Advances in Immunotherapy and Therapeutic Strategies.
肝细胞癌(HCC)是全球癌症相关死亡的主要原因。
肝细胞癌(HCC)是全球癌症相关死亡的主要原因。传统疗法常受限于肿瘤异质性和免疫抑制性肿瘤微环境(TME)。树突状细胞(DC)是协调抗肿瘤免疫的核心,已成为HCC免疫治疗的关键靶点。本综述探讨了DC亚群(cDC1、cDC2、pDC和moDC)的生物学功能及其在启动和调节抗HCC免疫应答中的作用。我们详细阐述了TME中DC功能受损的机制,包括调节性T细胞(Treg)、髓源性抑制细胞(MDSC)、肿瘤相关巨噬细胞(TAM)和癌症相关成纤维细胞(CAF)的抑制作用。此外,我们讨论了基于DC的新型治疗策略,如旨在增强抗原呈递和T细胞活化的DC疫苗。将DC疫苗与免疫检查点抑制剂(ICI),包括PD-1/PD-L1和CTLA-4阻断剂联合使用,显示出协同效应,可克服免疫逃逸并改善临床结局。尽管取得了进展,但DC亚群异质性、TME复杂性和患者变异性等挑战仍需要进一步优化和个性化DC治疗方案。未来研究应聚焦于完善这些策略,利用基因组分析和人工智能等先进技术,以最大化治疗效果并革新HCC治疗。通过恢复DC功能和重编程TME,基于DC的免疫治疗具有巨大潜力来改变HCC的管理并改善患者生存。
Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide. Conventional therapies are frequently limited by tumor heterogeneity and the immunosuppressive tumor microenvironment (TME). Dendritic cells (DCs), central to orchestrating antitumor immunity, have become key targets for HCC immunotherapy. This review examines the biological functions of DC subsets (cDC1, cDC2, pDC, and moDC) and their roles in initiating and modulating immune responses against HCC. We detail the mechanisms underlying DC impairment within the TME, including suppression by regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and cancer-associated fibroblasts (CAFs). Additionally, we discuss novel DC-based therapeutic strategies, such as DC-based vaccines designed to enhance antigen presentation and T cell activation. Combining DC vaccines with immune checkpoint inhibitors (ICIs), including PD-1/PD-L1 and CTLA-4 blockers, demonstrates synergistic effects that can overcome immune evasion and improve clinical outcomes. Despite progress, challenges related to DC subset heterogeneity, TME complexity, and patient variability require the further optimization and personalization of DC-based therapies. Future research should focus on refining these strategies, leveraging advanced technologies like genomic profiling and artificial intelligence, to maximize therapeutic efficacy and revolutionize HCC treatment. By restoring DC function and reprogramming the TME, DC-based immunotherapy holds immense potential to transform the management of HCC and improve patient survival.
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