| First Author | Oka T | Year | 2025 |
| Journal | J Clin Invest | Volume | 135 |
| Issue | 1 | PubMed ID | 39744942 |
| Mgi Jnum | J:360336 | Mgi Id | MGI:7798715 |
| Doi | 10.1172/JCI183274 | Citation | Oka T, et al. (2025) T helper 2 cell-directed immunotherapy eliminates precancerous skin lesions. J Clin Invest 135(1) |
| abstractText | 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. Calcipotriol-plus-5-FU immunotherapy was dependent on IL-24 to suppress skin carcinogenesis in vivo. Collectively, our findings establish a critical role for Th2 immunity in cancer immunoprevention and highlight the Th2/IL-24 axis as an innovative target for skin cancer prevention and therapy. |
