Immune response associated with nonmelanoma skin cancer.
It is now clear that UV radiation causes nonmelanoma skin cancer in at least two ways: by causing permanent changes in the genetic code and by preventing immunologic recognition of mutant cells. These are interacting rather than separate mechanisms. Damage to DNA results in disregulation of cellular proliferation and initiates immune suppression by stimulating the production of suppressive cytokines. These cytokines contribute to the loss of immunosurveillance. Ultraviolet radiation has both local and systemic immunosuppressive effects. Locally, it depletes and alters antigen-presenting LC at the site of UV irradiation. Systemic suppression results when Ts cells are induced, by altered LC, by inflammatory macrophages that enter the skin following UV irradiation, or by the action of cytokines. Damage to DNA appears to be one of the triggering events in inducing systemic immunosuppression via the release of immunosuppressive cytokines and mediators. Immunologic approaches to treating skin cancers so far have concentrated on nonspecifically stimulating immune cells that infiltrate these tumors, but induction of specific immune responses against these tumors with antitumor vaccines has received little attention as yet. Preventive measures include sun avoidance and the use of sunscreens to prevent DNA damage by UV light. Future strategies may employ means to reverse UV-induced immunosuppression by using anti-inflammatory agents, biologicals that accelerate DNA repair or prevent the generation of immunosuppressive cytokines, and specific immunotherapy with tumor antigens. New approaches for studying the immunology of human skin cancers are needed to accelerate progress in this field.
Strickland
F M
FM
Department of Immunology, University of Texas, M. D. Anderson Cancer Center, Houston, USA.
Kripke
M L
ML
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000528:radiation effects; D002280:Basal Cell Carcinoma / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D002465:Cell Movement / Q000528:radiation effects; D016207:Cytokines / Q000276:immunology; D004249:DNA Damage; D006801:Humans; D007108:Immune Tolerance; D012867:Skin / Q000276:immunology / Q000473:pathology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D014466:Ultraviolet Rays / Q000009:adverse effects
D016207:Cytokines