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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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49th Annual ESDR Meeting

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Abstract

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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© Copyright 2019 Morressier GmbH.
All rights reserved.