METHODS: We investigated the synergistic effect of Drp1-mediated T cell antitumor activities and programmed cell death protein 1 (PD-1) blockade for treating lung cancer through in vitro co-culture experiments and an in vivo nude mouse xenograft model.
RESULTS: High expression levels of Drp1 positively regulated T cell activation, enhanced T cell-induced suppression of lung cancer cells, promoted CD8+ T cell infiltration in the tumor and spleen, and significantly enhanced the antitumor immune response of the PD-1 inhibitor pembrolizumab. The mechanism of this synergistic antitumor effect involved the secretion of immune killing-related cytokines and the regulation of the PD-1-ERK/Drp1 pathway in T cells.
CONCLUSIONS: Our findings suggest that modifying Drp1 expression in T cells could serve as a potential therapeutic target for enhancing the antitumor immune response in future immunotherapies.
方法:我们通过体外共培养实验和体内裸鼠异种移植模型研究了Drp1介导的T细胞抗肿瘤活性和程序性细胞死亡蛋白1(PD-1)阻断治疗肺癌的协同作用。
结果:Drp1的高表达水平正调节T细胞活化,增强T细胞诱导的肺癌细胞抑制,促进肿瘤和脾脏中的CD8+T细胞浸润,并显著增强PD-1抑制剂派姆单抗的抗肿瘤免疫反应。这种协同抗肿瘤作用的机制涉及免疫杀伤相关细胞因子的分泌和T细胞中PD-1-ERK/Drp1途径的调节。
结论:我们的研究结果表明,修饰T细胞中的Drp1表达可以作为未来免疫疗法中增强抗肿瘤免疫应答的潜在治疗靶点。