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

• Published in: International immunopharmacology Vol. 105; p. 108551
• Main Authors: Chen, Yanxin, Liu, Yunwei, Xiong, Xiaoliang, Zeng, Zhimin, Luo, Daya, Liu, Anwen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2022; Elsevier BV
• Subjects: Animals; Apoptosis; Carcinoma, Lewis Lung - drug therapy; Cardiac injury; Cell death; Drug-Related Side Effects and Adverse Reactions - etiology; Echocardiography; Fibrosis; Heart; Heart function; Histopathology; Immune checkpoint inhibitor; Immune Checkpoint Inhibitors; Immune response; Immunohistochemistry; Immunotherapy; Immunotherapy - methods; Immunotherapy-related adverse effects; Inflammation; Inflammatory response; Inhibitors; Intestine; Kidneys; Lung cancer; Lung Neoplasms - drug therapy; Mice; Organs; Pathological injury; PD-1 inhibitor; PD-1 protein; Spleen; Staining; Tumors; Immunotherapy-related adverse effects; Pathological injury; PD-1 inhibitor; Immune checkpoint inhibitor; Cardiac injury
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2022.108551

•Immunotherapy-related adverse effects (irAEs) are the main obstacle to immunotherapy for malignant tumors.•There is currently a lack of irAE mouse models and pathological damaged data.•We described the irAEs that cause multiorgan pathological damage in a holistic manner in a Lewis tumor mouse model, providing information for clinical diagnosis and treatment. 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.