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. 1998 Jan 1;101(1):33–39. doi: 10.1172/JCI1165

Sunlight-induced basal cell carcinoma tumor cells and ultraviolet-B-irradiated psoriatic plaques express Fas ligand (CD95L).

C Gutierrez-Steil 1, T Wrone-Smith 1, X Sun 1, J G Krueger 1, T Coven 1, B J Nickoloff 1
PMCID: PMC508537  PMID: 9421463

Abstract

The skin is constantly exposed to sunlight and frequently develops sun-induced skin cancers such as basal cell carcinoma (BCC). These epidermal-derived tumors escape local immune surveillance and infiltrate the dermis, requiring surgical removal. We report here that in contrast to keratinocytes in normal skin (n = 4), BCC tumor cells (n = 6) strongly 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, CD95L can be induced on normal cultured keratinocytes after exposure to ultraviolet-B light (UV-B) irradiation. This induction of CD95L was confirmed at the mRNA and protein levels using multipassaged human keratinocytes and a keratinocyte cell line. Keratinocytes induced to express CD95L acquired the functional capacity to kill a CD95-positive lymphocyte cell line. Whereas hyperplastic keratinocytes in untreated psoriatic plaques do not express CD95L on their plasma membrane, after UV-B treatment there is strong and diffuse keratinocyte CD95L expression that coincided in a temporal fashion with depletion of intraepidermal T cells in all five patients studied. Our data suggest a novel molecular pathway by which UV light can contribute to the ability of a skin cancer to escape from immune attack by cytotoxic T lymphocytes, and a previously unrecognized therapeutic mechanism of action for UV-B light in psoriasis via keratinocyte CD95L expression. Such immunological events involving CD95L provide new insight and opportunity for novel treatment approaches not only for cutaneous neoplasms but also for various T cell-mediated dermatoses such as psoriasis.

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Selected References

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