title: The immune system and skin cancer.
abstract: Carcinogenesis involves multiple mechanisms that disturb genomic integrity and encourage abnormal proliferation. The immune system plays an integral role in maintaining homeostasis and these mechanisms may arrest or enhance dysplasia. There exists a large body of evidence from organ transplantation literature supporting the significance of the immune suppression in the development of skin cancer. Nonmelanoma skin cancers are the most frequent neoplasms after organ transplantation, with organ transplant recipients having a 65-fold increase in squamous cell carcinoma incidence and 10-fold increase in basal cell carcinoma incidence. Similarly, UV-radiation (UVR) induced immunosuppression is correlated with the development of cutaneous malignancies in a dose-dependent manner. This was first shown several decades ago by Margaret Kripke, when transplanted tumors were rejected in mice with competent immune systems, but grew unchecked in immunosuppressed specimens. After UV exposure, chromophores initiate a cascade that leads to immunosuppression via derangement of Langerhans cells' antigen-presenting capacity. UV-irradiated Langerhans cells present antigens to Th2 cells, but fail to stimulate Th1 cells. A subset of T regulatory cells, specific for the antigen encountered after UVR, is also stimulated to proliferate. In general UV irradiation leads to a greater number of T regulatory cells and fewer effector T cells in the skin, shiftingthe balance from T-cell-mediated immunity to immunosuppression. These regulatory cells have the phenotype CD4+, CD25+, Foxp3+, CTLA-4+. These and many other changes in local immunity lead to a suppressed immune state, which allow for skin cancer development.
authors.forename: Sherry H
authors.initials: SH
authors.lastname: Yu
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Bordeaux
authors.forename: Elma D
authors.initials: ED
authors.lastname: Baron
mesh_terms: D002280:Basal Cell Carcinoma / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation / Q000528:radiation effects; D006801:Humans; D007107:Immune System / Q000528:radiation effects*; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D015994:Incidence; D008213:Lymphocyte Activation / Q000528:radiation effects; D016377:Organ Transplantation; D012867:Skin / Q000276:immunology / Q000473:pathology; D012878:Skin Neoplasms / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology / Q000528:radiation effects*; D014466:Ultraviolet Rays