Retinoic acid protests Langerhans' cells from the effects of the tumour promoter 12-O-tetradecanoylphorbol 13-acetate

Retinoic acid prevents the decrease in epidermal Langerhans' cell (LC) density which occurs upon application of the tumour promotor 12-O-tetradecanoylphorbol 13-acetate (TPA) to murine skin. This occurred very rapidly, after only 1 week, and was still observed after 4 weeks of treatment. Retinoic acid alone increased the LC density, indicating that it could affect LC density independently of TPA. The induction of a contact sensitivity response which was inhibited by prior treatment with TPA due to the low LC density was also protected by retinoic acid. The anti-carcinogenic activity of retinoic acid is partially the result of its ability to inhibit tumour promotion. The loss of LC may be one of the important steps in tumour promotion as this would allow developing tumours to escape immune destruction. Our studies suggest that the ability of retinoic acid to suppress tumour promotion may be in part by protecting local antigen-presenting cells, thus allowing an immune response to be generated against tumours.