798 Interleukin-17 pathway activation in radiation dermatitis

Each year, 10 million cancer patients are treated with radiotherapy (RT) worldwide. RT is paramount in treatment, however up to 95% of develop radiation dermatitis (RD). Patients RD painful skin breakdown, which can be therapy limiting and detrimental quality life. No evidence-based standard for the management exists, highlights inadequate understanding its pathogenesis. The pro-inflammatory cytokine interleukin-17 (IL-17) known play a role numerous inflammatory conditions. As preclinical studies suggest that IL-17 upregulated murine models, we examined pathway activation RD. Using model receiving single dose 25 Gy, demonstrated strong correlation between target gene upregulation increased severity irradiated via qRT-PCR (p < 0.001). Additionally, utilized cell RNA-sequencing (scRNA-seq) profile cells from sham identified novel keratinocyte subtype exclusive group abundant Receptor Type C (IL-17RC) expression. Both genetic knockout IL-17RC blocking IL-17A, ligand IL-17RC, neutralizing antibody independently prevented severe models. Finally, confirmed IL-17A human stratum corneum using tape strip expression profiling, non-invasive sample collection method analysis. With IRB approval, collected samples (n=6) ≥15 fractions breast before after patient arm breast. Tape-strip gene-expression profiling was conducted qRT-PCR, revealed induction an by 12.18-fold on average (p< 0.05 one sided paired t-test). These results support development provide basis future clinical trials investigating anti-IL17 therapies