Sun-damaged skin harbors areas of normal epidermis mixed with areas of actinic keratosis, composed of transformed keratinocytes with dysregulated proliferation and differentiation, due to UV-induced somatic mutations. Topical calcipotriol induces TSLP production by transformed keratinocytes in actinic keratosis but not in unaffected keratinocytes. TSLP is recognized by T cells in the dermis and stimulates Th2 differentiation. Keratinocyte injury, mediated by the chemotherapeutic agent 5-FU, leads to expression of damage-associated molecular patterns including Annexin A1, Calreticulin, and MHC class II, which further promote T cell activation and proliferation. Activated Th2 cells secrete IL-4 and IL-13, which specifically stimulate transformed keratinocytes to express IL-24. IL-24 acts in an autocrine and paracrine fashion on transformed keratinocytes to enhance apoptosis, autophagy, and general cell death. In addition, ongoing stimulation of dermal T cells facilitates development of resident memory T cells (TRM) in the skin, allowing for long-term immunosurveillance and elimination of squamous cell carcinoma and its precursors.