861 EGFR/MEK inhibitor therapy induces partial hair follicle immune privilege collapse in vivo and ex vivo

Epidermal growth factor receptor inhibitors(EGFRi) and Mitogen Activated Kinase inhibitors(MEKi) induce a folliculitis in 65-80% of patients, but it is unclear how they impact on the human hair follicle(HF). We have asked whether EGFRi/MEKi-induced associated with damage HFs immune privilege(IP) excessive HF secretion pro-inflammatory mediators. Scalp biopsies were taken from EGFRi-treated patients exhibiting compared to normal scalp skin(n=9). Ex vivo, organ-cultured exposed EGFRi(5μM Erlotinib) or MEKi(Cobimetinib 1μM)(n=5 each). Our results showed that, EGFRi significantly induce:(1) characterized, by dense infiltrates T cells(CD4+, CD8+), macrophages(CD68+), neutrophils mast cells around bulge infundibulum (Immunohistochemistry(IHC));(2) upregulation MHC class I II, ß2-microglobulin, downregulation TGF-ß1, while CD200 expression was unaffected PD-L1 even upregulated (Immunoflourescence (IF)) (3) increased IL-33 decreased IL-37 transcriptional (RNAseq in-situ hybridization (ISH)). inhibition EGFR-MEK-ERK pathway significant:(1) dysregulation, at 24hrs, IP-related transcripts including an increase decrease TGFβ-1 mRNA(RNAseq);(2) protein (72 h), TGF-ß1 attenuated (IF) expression/secretion (Luminex analysis, ISH RNAseq) (All p<0.05). Thus, EGFRi/MEKi induces partial IP collapse vivo ex vivo. Future management should focus restoring IP, inhibiting anti-inflammatory interlukin IL-37.