SUNLIGHT-INDUCED BASAL-CELL CARCINOMA TUMOR-CELLS AND ULTRAVIOLET-B-IRRADIATED PSORIATIC PLAQUES EXPRESS FAS LIGAND (CD95L)

The skin is constantly exposed to sunlight and frequently develops sun -induced skin cancers such as basal cell carcinoma (BCC), These epider mal-derived tumors escape local immune surveillance and infiltrate the dermis, requiring surgical removal, We report here that in contrast t o keratinocytes in normal skin (n = 4), BCC tumor cells (n = 6) strong ly and diffusely express Fas ligand (CD95L), but not Fas antigen (CD95 ). This CD95L expression in vivo by BCC tumor cells is associated with peritumoral T lymphocytes that are undergoing apoptosis, Moreover, CD 95L can be induced on normal cultured keratinocytes after exposure to ultraviolet-B light (UV-B) irradiation. This induction of CD95L was co nfirmed at the mRNA and protein levels using multipassaged human kerat inocytes and a keratinocyte cell line, Keratinocytes induced to expres s CD95L acquired the functional capacity to kill a CD95-positive lymph ocyte cell line, Whereas hyperplastic keratinocytes in untreated psori atic plaques do not express CD95L on their plasma membrane, after UV-B treatment there is strong and diffuse keratinocyte CD95L expression t hat coincided in a temporal fashion with depletion of intraepidermal T cells in all five patients studied, Our data suggest a novel molecula r pathway by which UV light can contribute to the ability of a skin ca ncer to escape from immune attack by cytotoxic T lymphocytes, and a pr eviously unrecognized therapeutic mechanism of action for UV-B light i n psoriasis via keratinocyte CD95L expression, Such immunological even ts involving CD95L provide new insight and opportunity for novel treat ment approaches not only for cutaneous neoplasms but also for various T cell-mediated dermatoses such as psoriasis.