Ying Shiding, Liu Haiyan, Zhang Yongliang, Mei Yu
Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore.
Vaccines (Basel). 2025 May 4;13(5):496. doi: 10.3390/vaccines13050496.
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.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因。传统疗法常常受到肿瘤异质性和免疫抑制性肿瘤微环境（TME）的限制。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针对HCC的免疫反应中的作用。我们详细阐述了TME内DC功能受损的机制，包括调节性T细胞（Tregs）、髓源性抑制细胞（MDSCs）、肿瘤相关巨噬细胞（TAMs）和癌症相关成纤维细胞（CAFs）的抑制作用。此外，我们讨论了基于DC的新型治疗策略，例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（ICIs）联合使用，包括PD-1/PD-L1和CTLA-4阻滞剂，显示出协同效应，可克服免疫逃逸并改善临床结果。尽管取得了进展，但与DC亚群异质性、TME复杂性和患者个体差异相关的挑战仍需要对基于DC的疗法进行进一步优化和个性化。未来的研究应集中在完善这些策略，利用基因组分析和人工智能等先进技术，以最大限度地提高治疗效果并彻底改变HCC的治疗方式。通过恢复DC功能和重新编程TME，基于DC的免疫疗法在改变HCC治疗管理和提高患者生存率方面具有巨大潜力。
