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 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.
Gutierrez-Steil
C
C
Department of Pathology and Skin Cancer Research Laboratories, Cardinal Bernardin Cancer Center, Loyola University of Chicago, Maywood, Illinois 60153, USA.
Wrone-Smith
T
T
Sun
X
X
Krueger
J G
JG
Coven
T
T
Nickoloff
B J
BJ
D000328:Adult; D000818:Animals; D002280:Basal Cell Carcinoma / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D013472:Sunlight; D013601:T-Lymphocytes / Q000166:cytology; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor