ABSTRACT
@#[摘 要] 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。
ABSTRACT
Gallbladder cancer (GBC) is the most common malignancy in the biliary tract. Without effective treatment, its prognosis is notoriously poor. Tea polyphenols (TPs) have many pharmacological and health benefits, including antioxidant, anti-inflammatory, anti-tumor, anti-thrombotic, antibacterial, and vasodilatory properties. However, the anti-cancer effect of TPs in human gallbladder cancer has not yet been determined. Cell viability and colony formation assay were used to investigate the cell growth. Cell cycle and apoptosis were evaluated by flow cytometry analysis. Western blot assay was used to detect the expression of proteins related to cell cycle and apoptosis. Human tumor xenografts were used to examine the effect of TPs on gallbladder cancer cells in vivo. TPs significantly inhibited cell growth of gallbladder cancer cell lines in a dose- and time-dependent manner. Cell cycle progression in GBC cells was blocked at the S phase by TPs. TPs also induced mitochondrial-related apoptosis in GBC cells by upregulating Bax, cleaved caspase-3, and cleaved PARP expressions and downregulating Bcl-2, cyclin A, and Cdk2 expressions. The effects of TPs on GBC were further proven in vivo in a mouse xenograft model. Our study is the first to report that TPs inhibit GBC cell growth and these compounds may have potential as novel therapeutic agents for treating gallbladder cancer.