Pan Yueh, Shih Hung-Jen, Chuang Shu-Han, Chang Chin-Pao, Hsiao Chi-Hao, Chiu Ya-Hsu, Wang Pai-Fu, Lin Chi-Chen, Shih Ping-Hsiao
Division of Urology, Department of Surgery, Changhua Christian Hospital, No.135 Nanhsiao Street, Changhua City, 50006, Taiwan.
Doctoral Program in Translational Medicine, National Chung Hsing University, No.145 Xingda Rd., South Dist, Taichung City, 402202, Taiwan.
BMC Cancer. 2025 Jun 1;25(1):980. doi: 10.1186/s12885-025-14383-7.
Results of previous studies have demonstrated that T-cell receptor cross-linking rapidly generates reactive oxygen species, which play essential signaling roles within mitochondria for the antigen-specific expansion of T-cells. However, oxidative stress also causes damage to cellular organelles. Thus, modulating ROS metabolism using antioxidants during naïve T-cell activation may promote the expansion and generation of functional T-cells. Notably, urothelial cancer is a sex-specific malignancy with high mortality rates worldwide. The present study aimed to evaluate the effects of various antioxidants on γδ T-cell proliferation, and the associated cytotoxicity against urothelial carcinoma cells (UCs).
Over a period of cell induction and expansion, peripheral blood mononuclear cells were cultured with or without different antioxidants, including N-acetyl cysteine (NAC), vitamin C and vitamin E. Subsequently, phenotypic characterization of γδ T-cells and their cytolytic effects against UCs were analyzed by flow cytometry and cell viability assays, respectively.
The results revealed that NAC partially inhibited T-cell expansion in a dose-dependent manner. In addition, CD3/Vγ9 levels and natural killer group 2D receptor expression were mildly reduced following treatment with a high dose of NAC, whereas CD3/CD56 levels and CD314 expression in natural killer-like cells were moderately decreased following treatment with vitamin E. Particularly, the direct co-incubation of bladder cancer cells with γδ T-cells supplemented with antioxidants significantly enhanced bladder cancer cytolysis. Collectively, results of the present study revealed that co-administration of functional antioxidants during γδ T-cell expansion may enhance the quality and efficacy of adoptive T-cell therapies for cancer treatment.
先前的研究结果表明，T细胞受体交联可迅速产生活性氧物质，其在线粒体内发挥重要的信号传导作用，以促进T细胞的抗原特异性扩增。然而，氧化应激也会对细胞器造成损伤。因此，在初始T细胞激活过程中使用抗氧化剂调节活性氧代谢可能会促进功能性T细胞的扩增和生成。值得注意的是，尿路上皮癌是一种具有性别特异性的恶性肿瘤，在全球范围内死亡率很高。本研究旨在评估各种抗氧化剂对γδT细胞增殖的影响，以及对尿路上皮癌细胞（UCs）的相关细胞毒性。
在细胞诱导和扩增期间，将外周血单个核细胞与不同的抗氧化剂（包括N-乙酰半胱氨酸（NAC）、维生素C和维生素E）一起培养或不添加抗氧化剂培养。随后，分别通过流式细胞术和细胞活力测定分析γδT细胞的表型特征及其对UCs的细胞溶解作用。
结果显示，NAC以剂量依赖的方式部分抑制T细胞扩增。此外，高剂量NAC处理后，CD3/Vγ9水平和自然杀伤细胞组2D受体表达略有降低，而维生素E处理后，自然杀伤样细胞中的CD3/CD56水平和CD314表达中度降低。特别是，将膀胱癌细胞与添加了抗氧化剂的γδT细胞直接共同孵育可显著增强膀胱癌细胞溶解。总体而言，本研究结果表明，在γδT细胞扩增期间联合使用功能性抗氧化剂可能会提高过继性T细胞癌症治疗的质量和疗效。
