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

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.