The development of anti-PD-1 antibody-induced spinal cord injury in bone marrow transplant C57BL/6 Rag1-/- mouse model

被引：0

作者：

Chen, Huachun ^{[1
]}

Lu, Zhouxiao ^{[1
]}

Ni, Xiaowei ^{[1
]}

Zhang, Hui ^{[2
]}

Chen, Guiyuan ^{[3
]}

Wu, Xiaoyu ^{[1
]}

Ding, Mingxing ^{[3
]}

机构：

[1] Jinhua Guangfu Canc Hosp, Dept Resp & Crit Care Med, Jinhua 321001, Zhejiang, Peoples R China

[2] Jinhua Food & Drug Inspect & Testing Res Inst, Inst Pharmacol, Jinhua 321002, Zhejiang, Peoples R China

[3] Jinhua Polytech, Sch Med, Jinhua 321007, Zhejiang, Peoples R China

来源：

IMMUNOTHERAPY | 2024年 / 16卷 / 14-15期

关键词：

anti-PD-1; cancer treatment; CD8(+) T-cell; perforin/GrB/PI-9/FasL pathway; Rag1(-/-) mouse; spinal cord injury; SAFETY; APOPTOSIS; PD-1; PEMBROLIZUMAB; NEUROSERPIN; EXPRESSION; INHIBITOR; NIVOLUMAB; CANCER; PROTEINASE-INHIBITOR-9;

D O I：

10.1080/1750743X.2024.2383557

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Aims: This paper was to scrutinize the toxicity mechanism of anti-programmed death 1 (anti-PD-1) therapy-caused spinal cord injury (SCI). Methods: Bone marrow transplant Rag1(-/-) mice were used to establish SCI model. Results: 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. Conclusion: These results may provide theoretical foundation for the clinical treatment of SCI caused by anti-PD-1.

引用

页码：975 / 985

页数：11

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