Langerhans cell alterations in cutaneous carcinogenesis.
Analysis of the early stages of experimental skin cancer in mice has demonstrated that complete chemical carcinogens (e.g. DMBA or benzo(a)pyrene) and tumour promoters (e.g. TPA) but not tumour initiators (e.g. urethane) deplete or functionally alter epidermal Langerhans cells (LC). These changes result in altered local immunity as antigen presentation through LC depleted skin results in either immune tolerance due to the generation of suppressor T cells or anergy. Parallel studies in sheep have shown that, following the application of DMBA, depletion of LC is due to increased migration of these cells from the skin whereas tumour initiators did not alter LC migration. Likewise benzo(a)pyrene did not trigger enhanced LC migration from the epidermis. Experiments in mice suggest that part of this increased migration after the application of DMBA is due to the carcinogen being handled as an antigen by the epidermal LC. However, this fails to explain the prolonged migration which follows. The implication of these studies is that early in carcinogenesis, altered immune function occurs as a result of LC depletion/modification, allowing aberrant cells to proliferate in the absence of immune destruction.
Muller
H K
HK
Department of Pathology, University of Tasmania, Hobart, Australia.
Dandie
G W
GW
Ragg
S J
SJ
Woods
G M
GM
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000276:immunology*