树突状细胞临床治疗实体瘤:峰回路转

Dendritic cells in the clinical treatment of solid tumors:turning the corner

肿瘤免疫细胞疗法展现了良好的临床抗肿瘤前景。树突状细胞(DC)识别肿瘤抗原作为机体免疫响应的关键起始步骤,捕获肿瘤抗原后分化成熟,在淋巴结将抗原信号提呈给CD4^(+)T细胞、CD8^(+)T细胞等免疫细胞,激发抗肿瘤效应,应用于肿瘤治疗,尤其是实体瘤,被寄予厚望。但由于实体瘤TME复杂的结构特点、DC和T/B细胞免疫响应的机制不清晰等问题犹如崇山峻岭摆在眼前,故未能形成关键理论和技术突破。以CAR-T细胞为代表的精准细胞免疫疗法已表现出优势,但仍面临抗原选择瓶颈。DC治疗性疫苗在临床试验中表现出良好的疗效和安全性,随着DC在TME中关键作用机制的进一步揭示,研究者的目光重新聚焦在DC抗肿瘤效应,推动着DC与其他手段的联合疗法、工程化DC疫苗等实体瘤治疗方案从基础向临床转化,目前正迈入DC临床治疗实体瘤的新阶段。本文系统地对DC治疗实体瘤的临床研究进展、实体瘤TME中DC的种类及其抗肿瘤机制、工程化DC疫苗,以及面临的挑战和应对策略等问题进行了评述。

Tumor immunocytotherapy has shown promising clinical prospects.Recognition of tumor antigens by dendritic cells(DCs)is a critical initiating step in immune response.After capturing tumor antigens,DCs differentiate into mature cells and present the antigen signals to immune cells such as CD4^(+)T and CD8^(+)T cells in the lymph nodes,thereby stimulating an anti-tumor effect.This approach holds great potential for tumor treatment,especially for solid tumors.However,the complex structure of the solid tumor microenvironment and unclear mechanisms of DC and T/B cell immune response present significant challenges in front of us;therefore,the key theoretical and technological breakthroughs have not been achieved yet.Despite the advantages demonstrated by precise cellular immunotherapy such as CAR-T cells,antigen selection remains a bottleneck in treating solid tumors.DC-based therapeutic vaccines have shown promising efficacy and safety in clinical trials.With further elucidation of the important mechanisms of DCs in the TME,researchers have refocused on the anti-tumor effects of DCs.This has prompted the clinical transformation of DC combination therapies and synthetic biology vaccines for the treatment of solid tumors.Currently,DC-based clinical treatments for solid tumors are entering a new stage.This article provides a comprehensive review of the progress in clinical research on DC-based therapy for solid tumors,the types of DCs in TME and their anti-tumor mechanisms,engineered DC vaccines,as well as the existing challenges and coping strategies.