Wang Zhaoyi, Diao Zhongqi, Zhang Yiyan, Liu Jiangying, Li Yeshan, Sun Zijin, Zhen Huimin, Wang Haojia, Yang Siyun, Wang Tieshan, Ni Lei
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Department of Cancer Research Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, China.
Front Immunol. 2025 Mar 27;16:1537398. doi: 10.3389/fimmu.2025.1537398. eCollection 2025.
Following the approval of Chimeric Antigen Receptor T-cell Immunotherapy(CAR-T) in multiple countries, the Food and Drug Administration (FDA) approved tumor-infiltrating lymphocytes (TILs) and T-cell receptor-engineered T cells (TCR-T) treatments this year. The utilization of adoptive immunotherapy in tumor treatment has become increasingly prominent. Optimizing the cytotoxic effects of immune cells under culture conditions represents a current hot research topic in this domain.
In the current experiment, we conducted heat treatment on Jurkat-derived T cells at 39°C. On this basis, we utilized nine distinct injectable solutions and over 70 monomer components of Traditional Chinese Medicine (TCM). Subsequently, we co-cultured these treated Jurkat cells with K562-eGFP cells, and the co-culture process was monitored in real-time using the IncuCyte live-cell analysis system. Equally important, we combined HiMAP high-throughput transcriptome sequencing, proteomics, and metabolomics for in-depth examination. We screened for compounds possessing anti-tumor properties and thoroughly investigated their mechanisms of action.
The findings indicated that heating treatment augmented the cytotoxic effect of Jurkat cells against malignant tumors, and the optimal effect was achieved when T cells were exposed to 39°C for a duration of 24 hours(48% increase in cell proliferation rate compared to 37°C treatment). By triggering the generation of heat shock proteins and facilitating mitochondrial energy supply, the 39°C treatment amplified the anti-tumor functions of T cells. By analyzing the data, we identified 3 injectable solutions and more than 20 effective monomers capable of further enhancing the tumor-killing ability of T cells. High-throughput transcriptomics studies disclosed that the combination of thermotherapy and TCM promoted Jurkat cell proliferation, activation, and cytotoxic functions of Jurkat cells, thereby activating the Regulation of mitotic cell cycle to exert anti-tumor effects. The integration of transcriptomic and proteomic data demonstrated that Shengmai Injection significantly enhances the tumor-killing effect of Jurkat cells by down-regulating the Regulation of Apoptosis and Regulation of mitotic cell cycle signaling pathways.
随着嵌合抗原受体T细胞免疫疗法（CAR-T）在多个国家获批，美国食品药品监督管理局（FDA）今年批准了肿瘤浸润淋巴细胞（TILs）和T细胞受体工程化T细胞（TCR-T）疗法。过继性免疫疗法在肿瘤治疗中的应用日益突出。在培养条件下优化免疫细胞的细胞毒性作用是该领域当前的一个热门研究课题。
在当前实验中，我们对源自Jurkat细胞的T细胞进行了39°C的热处理。在此基础上，我们使用了九种不同的可注射溶液和70多种中药单体成分。随后，我们将这些经过处理的Jurkat细胞与K562-eGFP细胞共培养，并使用IncuCyte活细胞分析系统对共培养过程进行实时监测。同样重要的是，我们结合了HiMAP高通量转录组测序、蛋白质组学和代谢组学进行深入研究。我们筛选出具有抗肿瘤特性的化合物，并深入研究了它们的作用机制。
研究结果表明，热处理增强了Jurkat细胞对恶性肿瘤的细胞毒性作用，当T细胞在39°C下暴露24小时时达到最佳效果（与37°C处理相比，细胞增殖率提高了48%）。通过触发热休克蛋白的产生并促进线粒体能量供应，39°C处理增强了T细胞的抗肿瘤功能。通过分析数据，我们确定了3种可注射溶液和20多种有效单体，它们能够进一步增强T细胞的杀瘤能力。高通量转录组学研究表明，热疗与中药的联合促进了Jurkat细胞的增殖、激活和细胞毒性功能，从而激活有丝分裂细胞周期调控以发挥抗肿瘤作用。转录组学和蛋白质组学数据的整合表明，生脉注射液通过下调细胞凋亡调控和有丝分裂细胞周期信号通路，显著增强了Jurkat细胞的杀瘤效果。
