The Development of Anti-PD-1 Antibody-induced Spinal Cord Injury in Bone Marrow Transplant C57BL/6 Mouse Model

Overview

Journal Immunotherapy

Specialties Allergy & Immunology
Pharmacology

Date 2024 Aug 8

PMID 39115961

Authors

Huachun Chen

Zhouxiao Lu

Xiaowei Ni

Hui Zhang

Guiyuan Chen

Xiaoyu Wu

Mingxing Ding

Affiliations

Soon will be listed here.

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.

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