815 T helper 2 cell immunity eliminates pre-cancerous skin lesions

Actinic keratosis (AK) is a precursor to cutaneous squamous cell carcinoma (SCC). Effective therapeutics eliminate AKs and prevent SCC are lacking. Long treatment durations severe side effects have limited the efficacy of cytotoxic AK treatments including 5-fluorouracil (5-FU) chemotherapy photodynamic therapy. Previously, we shown that thymic stromal lymphopoietin (TSLP), an epithelium-derived cytokine, induces robust antitumor immunity in skin. Since this discovery, demonstrated high calcipotriol, topical TSLP inducer, combination with as novel immunotherapy for potential prevention. Here, investigated underlying mechanism resulted synergism between calcipotriol 5-FU. In conjunction induction, identified several Damage-associated molecular patterns (DAMPs) HLA class II be highly induced premalignant keratinocytes upon plus 5-FU treatment, which led massive infiltration by T helper 2 (Th2)-polarized CD4+ cells. Using Il4ra knockout mice adoptive transfer models, showed Th2 polarization was required cells were sufficient TSLP-mediated RNA sequencing multiplex immunostaining revealed interleukin (IL)-24 upregulated specifically after Immunotherapy. As effector molecule, IL-24 known induce apoptosis toxic autophagy cancer-selective manner. cytokines expression vitro. Importantly, overexpression caused cytotoxicity These findings reveal mode against premalignancy broad implications cancer immunoprevention.