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Human hair follicles express PD-L1, whose expression is down-regulated by EGFR and MEK inhibitors ex vivo. A potential mechanism for EGFR inhibitor induced sterile folliculitis.


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Presented at

49th Annual ESDR Meeting





Epidermal growth factor receptor inhibitors (EGFRi) and mitogen activated protein kinase inhibitors (MEKi) are commonly used in oncology. They are associated with adverse cutaneous reactions in 80% of patients. These reactions can be divided into on-target pharmacodynamic effects, specifically inhibition of keratinocyte cell proliferation, and pro-inflammatory effects which culminate in a sterile folliculitis. EGFRi and MEKi are known to inhibit an immune checkpoint inhibitor, Programme Death Ligand 1 (PD-L1), whose down-regulation might contribute to this inflammatory reaction. Our objectives were to: 1) characterize the location of PD-L1 in human scalp skin; and 2) evaluate cutaneous changes in PD-L1 expression following EGFRi or MEKi. In normal human scalp skin (n= 3 males; mean age 58) PD-L1 expression was localized histologically in immune cells within the dermis as well as in the bulge and pre-cortical hair matrix of the hair follicle (HF). To evaluate the effect of EGFRi and MEKi on PD-L1, human facial skin was organ cultured with control, Erlotinib (EGFRi) or Cobimetinib (MEKi). We demonstrated that after 3 days of organ culture the assay recapitulated expected pharmacodynamic effects, namely a significant decrease in keratinocyte proliferation in the basal layer of the epidermis and in the hair matrix (n=5 , p<0.05). Most importantly, we demonstrated that gene expression of PD-L1 was significantly decreased after 24hrs (n=3, p<0.05). We are currently investigating whether this process is linked to a collapse in the HF immune privilege. In conclusion, we have shown that human HFs prominently express PD-L1 and that following EGFR or MEK inhibition cutaneous expression is down-regulated inviting the hypothesis that this could contribute to the sterile folliculitis seen in EGFRi or MEKi treated patient


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All rights reserved.