Clinical inhibition of the epidermal growth factor receptor (EGFR) results in stereotypic papulopustular eruptions, bacterial superinfection of the skin with Staphylococcus aureus (S. aureus) and diarrhea. These stigmatizing side effects severely deteriorate patients’ wellbeing and therapy adherence. Hence, the identification and characterization of EGFR dependent anti-microbial defense mechanisms is of utter importance to improve our capability to treat those adverse barrier effects to increase patients’ quality of life and enhance EGFR targeted cancer therapy efficacy. Applying EGFR skin deficient mouse models, we could recapitulate EGFR -I induced skin abnormalities. We identified the initial inflammatory trigger within the outgrowing commensal bacterial skin community. EGFR deficient skin is dominated first by commensal Staphylococci species such as S. xylosus which then shifts to a pathogenic S. aureusdriven dysbiosis analogous to S. aureus superinfection in human EGFR-I treated patients. Immunological assessment together with 16S microbial rRNA sequencing revealed that EGFR deficient skin is permissive for microbial outgrowth because of barrier integrity loss and reduction of anti-microbial defense capacity. We now use a combination of single cell RNA sequencing and targeted EGFR depletion mouse models to identify the cell population and the molecular mechanism, which is responsible for microbial regulation and barrier defense. In summary, we could identify a crucial EGFR regulated microbial gate keeper function at the hair follicle, which is perturbed during targeted anti-cancer therapy. We now aim to identify its molecular mechanism in order to improve the efficiency of cancer therapies and treat acneiform skin inflammation in general.

ESDR352 - Targeted inhibition of EGFR reduces anti-microbial defense mechanisms at the skin barrier

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.