Tobacco smoke condensate cutaneous carcinogenesis: changes in Langerhans cells and tumor regression

Tobacco smoke condensate was painted on the skin of BALB/c mice. It increased the density and changed the morphology of Langerhans' cells (LC). LC number in epidermal sheets of treated mice was significantly higher (1793 LC/mm2) than in controls (946 LC/mm2) (P < 0.0001) and remained elevated for 35 weeks. LC became less dendritic, or even rounded in shape, and smaller in size. The function of the morphologically altered LC was impaired when assessed by the contact hypersensitivity response. These changes were associated with skin tumour development in all treated mice. Ten weeks after stopping the TSC treatment, LC number in skin tumours and in skin around these lesions had not decreased, but significantly increased (P < 0.0001). During this period tumour regression occurred in 23% of tumours; the remaining tumours showed a 50% reduction in size. At 45 weeks, the LC number in epidermal sheets around skin papillomas was 2274 ± 14.14/mm2 and in invasive squamous cell carcinomas was 2088 ± 183/mm2. This was associated with reversible changes in LC morphology, where cells became fully dendritic. This also correlated with lymphocytic infiltration into tumours, tumour necrosis, reduction in tumour size and/or tumour regression. It is concluded that the influx of normal LC into the skin tumours allowed the development of an immune response with tumour regression.