Carcinogen-induced depletion of cutaneous Langerhans cells.

The chemical carcinogen 7,12-dimethylbenz (a) anthracene (DMBA) is a potent carcinogen which, when applied to the skin of BALB/c mice weekly for 7-8 weeks, causes the induction of macroscopically visible skin tumours. We report that DMBA also depletes Langerhans cells (LC) from treated skin; the number of cutaneous LC is reduced by nearly 50% 3 days after the first application of DMBA, and continues to decrease upon further treatment. After 7-8 weeks of DMBA application, while tumours are becoming macroscopically visible, there is a considerably lower LC density in treated skin. Upon cessation of the DMBA treatment, the LC repopulate the skin, returning to control values within 55-64 days. During this repopulation of the skin by LC, the tumours begin to decrease in size. Since LC function as local cutaneous antigen-presenting cells, and are responsible for initiation of an immune response against antigens in the skin, their depletion during tumour induction may allow DMBA-transformed cells to circumvent the immune system and form tumours. Their reappearance associated with tumour regression suggests that the LC are involved in an immune response against the tumours.