T helper 2 cell-directed immunotherapy eliminates precancerous skin lesions.

ABSTRACT: The continuous rise in skin cancer incidence highlights an imperative for improved skin cancer prevention. Topical calcipotriol-plus-5-fluorouracil (calcipotriol-plus-5-FU) immunotherapy effectively eliminates precancerous skin lesions and prevents squamous cell carcinoma (SCC) in patients. However, its mechanism of action remains unclear. Herein, we demonstrate that calcipotriol-plus-5-FU immunotherapy induces T helper type 2 (Th2) immunity, eliminating premalignant keratinocytes in humans. CD4+ Th2 cells were required and were sufficient downstream of thymic stromal lymphopoietin cytokine induction by calcipotriol to suppress skin cancer development. Th2-associated cytokines induced IL-24 expression in cancer cells, resulting in toxic autophagy and anoikis followed by apoptosis. Calcipot

SUBMITTER: Oka T 

PROVIDER: S-EPMC11684800 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature