Immune Profiling of Dermatologic Adverse Events from Checkpoint Blockade using Tissue Cyclic Immunofluorescence

Abstract

In this study, we demonstrate the utility of whole-slide CyCIF (tissue-based cyclic immunofluorescence) imaging for characterizing immune cell infiltrates in immune checkpoint inhibitor (ICI)-induced dermatologic adverse events (dAEs). We analyzed six cases of ICI-induced dAEs, including lichenoid, bullous pemphigoid, psoriasis, and eczematous eruptions, comparing immune profiling results obtained using both standard immunohistochemistry (IHC) and CyCIF. Our findings indicate that CyCIF provides more detailed and precise single-cell characterization of immune cell infiltrates than IHC, which relies on semi-quantitative scoring by pathologists. This pilot study highlights the potential of CyCIF to advance our understanding of the immune environment in dAEs by revealing tissue-level spatial patterns of immune cell infiltrates, allowing for more precise phenotypic distinctions and deeper exploration of disease mechanisms. By demonstrating that CyCIF can be performed on friable tissues, such as bullous pemphigoid, we provide a foundation for future studies to examine the drivers of specific dAEs using larger cohorts of phenotyped toxicity and suggest a broader role for highly multiplexed tissue imaging in phenotyping the immune mediated disease that they resemble.