Type 2 immunity links eczematous and lichenoid eruptions caused by immune checkpoint inhibitors.

Abstract

Cutaneous immune-related adverse events (cirAEs) induced by immune checkpoint inhibitor (ICI) therapy share clinical features with spontaneous inflammatory dermatoses. However, the exact immunopathogenesis of cirAEs remains unclear. To investigate the inflammation that mediates the most common cirAEs, lichenoid eruption (LE) and eczematous eruption (EE). In a prospective cohort study, participants with cancer on ICI therapy with any clinically visible cirAEs were enrolled. T helper-1 (Th1) and Th2 cell responses in cirAEs were compared to spontaneous lichenoid dermatitis and eczematous dermatitis. Among 88 cirAE biopsies collected, LE (35.22%) and EE (31.81%) accounted for most cases. In contrast to lichenoid dermatitis, we found that the CD4⁺/CD8⁺ T-cells and Th2/Th1 ratios were increased in ICI-induced LE, similar to EE. Importantly, we identified several cirAEs displaying a combination of LE and EE on pathology. Only the most common types of cirAEs were evaluated, and Th17 cells were not analyzed. Our findings indicate that LE and EE may represent a cirAE spectrum with a common underlying immunologic mechanism. Thus, understanding the immunopathogenesis of cirAEs can aid in their treatment and prevention.