A Novel Potential Role for Monocytes Revealed by Single Cell Analysis of Immunotherapy Induced Immune Related Adverse Events

SIMPLE SUMMARY: Immunotherapy treatments have become one of the most popular options in cancer care. While their efficacy is well established, there is a significant risk of a variety of immune based side effects. These side effects, usually referred to as immune related adverse events, are well documented but poorly understood. To improve our understanding of the key cellular players involved in the development of these side effects, we have analyzed single cell sequencing data from PBMCs drawn from patients who developed skin immune related adverse events. Using that data, we have identified cellular population dynamic trends which point to potential mechanisms and pathways through which the side effects are occurring. This research is an important step in improving our understanding of the mechanisms that drive immune related adverse events. ABSTRACT: Immune related adverse events (irAEs) are one of the leading causes of discontinuation of cancer immunotherapy treatment. Despite extensive research into the frequency and types of irAEs, little is known about the cell types and pathways through which these drugs cause the observed side effects. To identify cell types and pathways of interest, we have analyzed single cell sequencing data of PBMCs from patients who developed skin irAEs as a result of their immunotherapy treatment. Using Azimuth’s cell type identification software for PBMCs and GSEA pathway analysis, we found macrophage cell populations and reactive oxygen species related pathways to be upregulated. These results provide important groundwork to build a complete picture of the mechanisms which cause irAEs and finding ways to more effectively treat them.