785 Single-cell transcriptomic profile of EGFR-deficient epidermal compartments during folliculitis

Cutaneous adverse events including papulopustular rash, pruritus and xerosis are common during treatment of cancer patients with drugs inhibiting the epidermal growth factor receptor (EGFR). These adverse events may negatively affect the outcome of the cancer therapy by requiring interruption of an otherwise effective treatment. Using a mouse model with conditional deletion of EGFR in epidermal cells, we have previously shown that skin barrier dysfunction is initiated during hair shaft emergence through the skin surface. The collapse of the follicular epidermal barrier is then allowing microbial invasion which initiates a detrimental inflammatory cascade. In order to identify mechanistic key players, we performed single-cell transcriptomic analysis of the full epidermal compartment including immune cells and hair follicles during hair shaft emergence in EGFR-deficient epidermis. We found remarkable transcriptomic changes in both keratinocyte and immune cell populations compared to wildtype littermates. Perturbations in the inner layers of the hair follicle point to the structural dysfunction of the follicular unit. Langerhans cells in the EGFR-deficient epidermis express more activation markers indicating them as first immune responders. Ultimately, we aim to identify the cellular and molecular key players for therapeutic intervention to ameliorate adverse events associated with EGFR-targeted cancer therapy and gain biologic insight into the process of hair shaft emergence.