抗 PD-1 抗体诱导骨髓移植 C57BL/6 小鼠模型脊髓损伤的发展。

The development of anti-PD-1 antibody-induced spinal cord injury in bone marrow transplant C57BL/6 mouse model.

机构信息

Department of Respiratory & Critical Care Medicine, Jinhua Guangfu Cancer Hospital, Jinhua, 321001, Zhejiang, China.

Institute of Pharmacology, Jinhua Food & Drug Inspection & Testing Research Institute, Jinhua, 321002, Zhejiang, China.

出版信息

Immunotherapy. 2024;16(14-15):975-985. doi: 10.1080/1750743X.2024.2383557. Epub 2024 Aug 8.

DOI:10.1080/1750743X.2024.2383557

PMID:39115961

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11486090/

Abstract

This paper was to scrutinize the toxicity mechanism of anti-programmed death 1 (anti-PD-1) therapy-caused spinal cord injury (SCI). Bone marrow transplant mice were used to establish SCI model. Anti-PD-1 results in SCI via CD8 T-cells activation, while excessive activation of CD8 T-cells further aggravated SCI. Both anti-PD-1 and the activation of CD8 T-cells induced the expression of apoptosis-related perforin, GrB and FasL, but suppressed PI-9 level. The opposite results were observed in the effects of neuroserpin on these factors. CD8 T-cells activation induced neurotoxicity via upregulation perforin, GrB and FasL and inhibiting PI-9. Additionally, neuroserpin suppressed CD8 T-cells activation via perforin/GrB/PI-9/FasL pathways. These results may provide theoretical foundation for the clinical treatment of SCI caused by anti-PD-1.

摘要

这篇论文旨在探究抗程序性死亡 1（anti-PD-1）治疗引起的脊髓损伤（SCI）的毒性机制。使用骨髓移植小鼠建立 SCI 模型。抗 PD-1 通过激活 CD8 T 细胞导致 SCI，而 CD8 T 细胞的过度激活进一步加重了 SCI。抗 PD-1 和 CD8 T 细胞的激活均诱导了凋亡相关的穿孔素、GrB 和 FasL 的表达，但抑制了 PI-9 水平。神经丝氨酸蛋白酶抑制剂在这些因素上的作用则相反。CD8 T 细胞的激活通过上调穿孔素、GrB 和 FasL 并抑制 PI-9 诱导神经毒性。此外，神经丝氨酸蛋白酶抑制剂通过穿孔素/GrB/PI-9/FasL 途径抑制 CD8 T 细胞的激活。这些结果可能为抗 PD-1 引起的 SCI 的临床治疗提供理论基础。