PD-1 inhibitor causes pathological injury to multiple organs in a Lewis lung cancer mouse model

Yanxin Chen; Yunwei Liu; Xiaoliang Xiong; Zhimin Zeng; Daya Luo; Anwen Liu

doi:10.1016/j.intimp.2022.108551

PD-1 inhibitor causes pathological injury to multiple organs in a Lewis lung cancer mouse model

Int Immunopharmacol. 2022 Apr:105:108551. doi: 10.1016/j.intimp.2022.108551. Epub 2022 Jan 22.

Authors

Yanxin Chen¹, Yunwei Liu¹, Xiaoliang Xiong², Zhimin Zeng¹, Daya Luo³, Anwen Liu⁴

Affiliations

¹ Department of Medical Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006, China; Jiangxi Key Laboratory of Clinical Translational Cancer Research, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006, China; Radiation Induced Heart Damage Institute of Nanchang University, Nanchang, Jiangxi Province 330006, China.
² Department of Pathology, School of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi Province 330006, China.
³ Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi Province 330006, China. Electronic address: luodaya@ncu.edu.cn.
⁴ Department of Medical Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006, China; Jiangxi Key Laboratory of Clinical Translational Cancer Research, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006, China; Radiation Induced Heart Damage Institute of Nanchang University, Nanchang, Jiangxi Province 330006, China. Electronic address: awliu666@163.com.

PMID: 35077961
DOI: 10.1016/j.intimp.2022.108551

Abstract

Recently, immunotherapy has become one of the most promising strategies in the treatment of malignant tumors. However, nonspecific immune activation may lead to immunotherapy-related adverse effects (irAEs). IrAEs involve almost all organs and may be life-threatening. However, current research on irAEs is scarce, and knowledge regarding histopathology is insufficient. In the present study, after Lewis lung cancer mouse model formation, the experimental group mice were intraperitoneally injected with a programmed cell death protein 1 (PD-1) inhibitor. Hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and Masson's trichrome staining were used to evaluate the pathological characteristics of the heart, lungs, spleen, intestines, kidneys, and liver. Echocardiography was used to evaluate heart function. The results showed that one or more inflammatory cells were positively expressed in each organ in the PD-1 inhibitor group. Compared to the control group, Masson's trichrome staining showedincreased fibrosis of the heart, spleen, and kidney in the PD-1 inhibitor group, and echocardiography also showed impaired cardiac function in the PD-1 inhibitor group. Thus, the PD-1 inhibitor-induced inflammatory response may beimplicated in the impairment of multiple murine organs. This is the first study to describe the pathological changes in multiple organs caused by PD-1 inhibitors in a holistic form.

Keywords: Cardiac injury; Immune checkpoint inhibitor; Immunotherapy-related adverse effects; PD-1 inhibitor; Pathological injury.

MeSH terms

Animals
Carcinoma, Lewis Lung* / drug therapy
Drug-Related Side Effects and Adverse Reactions* / etiology
Immune Checkpoint Inhibitors
Immunotherapy / methods
Lung Neoplasms* / drug therapy
Mice

Substances

Immune Checkpoint Inhibitors