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

IF 2.7 4区医学 Q3 IMMUNOLOGY

Immunotherapy Pub Date : 2024-01-01 Epub Date: 2024-08-08 DOI:10.1080/1750743X.2024.2383557

Huachun Chen, Zhouxiao Lu, Xiaowei Ni, Hui Zhang, Guiyuan Chen, Xiaoyu Wu, Mingxing Ding

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引用次数: 0

Abstract

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.

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骨髓移植 C57BL/6 Rag1-/- 小鼠模型中抗 PD-1 抗体诱导的脊髓损伤的发展。

目的：本文旨在研究抗程序性死亡1（anti-PD-1）疗法导致脊髓损伤（SCI）的毒性机制。方法：采用骨髓移植 Rag1-/- 小鼠建立 SCI 模型。结果抗 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 细胞的激活都会诱导与细胞凋亡相关的穿孔素、GrB 和 FasL 的表达，但会抑制 PI-9 的水平。神经生长因子对这些因子的影响则与之相反。CD8+ T细胞活化通过上调穿孔素、GrB和FasL以及抑制PI-9诱导神经毒性。此外，神经生长因子还能通过穿孔素/GrB/PI-9/FasL途径抑制 CD8+ T 细胞的活化。结论这些结果可为抗PD-1引起的SCI的临床治疗提供理论依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunotherapy 医学-免疫学

CiteScore

5.00

自引率

3.60%

发文量

113

审稿时长

6-12 weeks

期刊介绍： Many aspects of the immune system and mechanisms of immunomodulatory therapies remain to be elucidated in order to exploit fully the emerging opportunities. Those involved in the research and clinical applications of immunotherapy are challenged by the huge and intricate volumes of knowledge arising from this fast-evolving field. The journal Immunotherapy offers the scientific community an interdisciplinary forum, providing them with information on the most recent advances of various aspects of immunotherapies, in a concise format to aid navigation of this complex field. Immunotherapy delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for this vitally important area of research. Unsolicited article proposals are welcomed and authors are required to comply fully with the journal''s Disclosure & Conflict of Interest Policy as well as major publishing guidelines, including ICMJE and GPP3.