Immune-Related Adverse Events of Immune Checkpoint Inhibitors—From a Clinical to Pathophysiological View

To the Editor We read with great interest the article published in JAMA Oncology by Berner and colleagues,¹ which was the first study, to our knowledge, to show a potential mechanism of skin immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs). Clinical studies have enhanced the understanding of irAEs in a clinical but not pathophysiological view. This study¹ found that patients with non–small cell lung cancer who were treated with a programmed cell death 1 (PD-1) inhibitor and experienced skin irAEs had a higher response rate and longer overall survival than those without skin irAEs. By analyzing the T-cell receptor (TCR) clones from peripheral blood mononuclear cells, tumor biopsy specimens, and biopsy specimens from the sites of skin irAEs, Berner et al¹ revealed that some shared antigens were present in both lung tumors and the skin. The study had meaningful findings, and we support most of the conclusions, but we have several concerns about the study.