1597 Topical calcipotriol plus 5-fluorouracil immunotherapy eliminates premalignant skin lesions through a T helper 2 cell/interleukin-24 axis

Actinic Keratoses (AKs) are premalignant intraepithelial skin lesions that can progress to cutaneous squamous cell carcinoma (SCC). The field of cancer immunotherapy has demonstrated the ability immune system treat late-stage cancers. We have shown also be leveraged prevent through a randomized, double-blind clinical trial. Topical calcipotriol plus 5-fluorouracil (5-FU) effectively eliminates AKs, leading SCC prevention in immunocompetent patients. Calcipotriol 5-FU activates robust CD4+ T helper 2 (Th2) immunity by inducing Thymic Stromal Lymphopoietin (TSLP) cytokine and stress signals keratinocytes. However, mechanism which activated Th2 cells eliminate AKs remains unknown. Herein, we investigated effector antitumor induced skin. RNA sequencing on trial samples revealed interleukin 24 (IL-24) was highly upregulated treated with compared alone. cell-derived cytokines, IL-4 IL-13, IL-24 expression lines. Intracellular induction lines resulted their apoptosis. To further investigate role downstream immunotherapy, developed Il24 knockout mice subjected them carcinogenesis protocol, mutant p53 clones resembling humans. Importantly, tumor protective effect markedly diminished mice. These findings reveal essential cell/IL-24 axis mediating function