(A) Diagram of sun-exposed human skin and SKH-1 mice treated with UV skin carcinogenesis protocol. DMBA, 7,12-dimethylbenz[a]anthracene. (B and C) Mutational signatures (B) and SNV counts per million (C) in human facial skin (n = 6) and UV-treated uninfected SKH-1 mouse back skin (n = 6). SNV, single-nucleotide variant. (D) Tumor burden at week 22 after UV treatment in CD8⁺ T cell–depleted (n = 9) versus IgG control (n = 19) uninfected SKH-1 mice. (E and F) Representative images of H&E-stained back skin (E) and CD8/CD3 immunofluorescently stained tumors (F) of UV-treated uninfected SKH-1 mice given anti-CD8 antibody (αCD8) or IgG control. (G) Mutational signatures in MmuPV1-infected (infected) and uninfected SKH-1 mice (n = 6 per group). Mutation type probabilities for uninfected mice are shown in B. Total mutation burden is comparable between UV-treated infected and uninfected mouse skin (3). (H and I) Representative images of H&E-stained (H) and CD8/CD3 immunofluorescently stained (I) back skin of MmuPV1-infected versus uninfected SKH-1 mice. (J) Quantified epidermal CD8⁺ T cells in MmuPV1-infected versus uninfected SKH-1 skin after UV treatment (n = 6 mice per group). T cells were counted in up to 10 randomly selected high-power fields (original magnification, ×200) per mouse. (K) Tumor burden at week 22 after UV treatment in CD8⁺ T cell–depleted (n = 7) versus IgG control (n = 16) MmuPV1-infected SKH-1 mice after UV treatment. (L and M) Representative images of H&E-stained back skin (L) and CD8/CD3 immunofluorescently stained tumors (M) of UV-treated MmuPV1-infected SKH-1 mice given αCD8 or IgG control. Dashed lines mark the epidermal basement membrane. Significance assessed by 2-tailed Mann-Whitney U test (C, D, and K) or 2-tailed unpaired t test (J). NS, not significant. Bar graphs show mean + SD. Scale bars: 1 mm (E and L) and 100 μm (F, H, I, and M).