由 Drp1 介导的增强的 T 细胞免疫活性可提高 PD-1 抑制剂治疗肺癌的疗效。
Enhanced T cell immune activity mediated by Drp1 promotes the efficacy of PD-1 inhibitors in treating lung cancer.
机构信息
Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, 110022, China.
Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441100, China.
出版信息
Cancer Immunol Immunother. 2024 Feb 10;73(2):40. doi: 10.1007/s00262-023-03582-5.
BACKGROUND
Dynamin-related protein 1 (Drp1)-mediated mitochondrial fission plays important roles in the activation, proliferation, and migration of T cells.
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.
背景
动力相关蛋白 1（Drp1）介导线粒体裂变在 T 细胞的激活、增殖和迁移中发挥重要作用。
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 细胞抗肿瘤活性与程序性死亡蛋白 1（PD-1）阻断协同作用治疗肺癌的效果。
结果
高表达水平的 Drp1 可正向调节 T 细胞的激活，增强 T 细胞对肺癌细胞的抑制作用，促进 CD8 T 细胞在肿瘤和脾脏中的浸润，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到免疫杀伤相关细胞因子的分泌和 T 细胞中 PD-1-ERK/Drp1 通路的调节。
结论
我们的研究结果表明，修饰 T 细胞中的 Drp1 表达可能成为未来免疫治疗中增强抗肿瘤免疫反应的潜在治疗靶点。
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