BIOACTIVE TUMOR-NECROSIS-FACTOR-ALPHA BUT NOT GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR CORRELATES INVERSELY WITH LANGERHANS CELL NUMBERS IN SKIN TUMORS

Langerhans' cells (LCs) are thought to play an important role in prese ntation of tumour antigens for the induction of anti-tumour immunity, Epidermis overlying some transplanted murine skin tumours contains inc reased numbers of LCs; however, alterations in LC numbers are not rela ted to tumour antigenicity or host immunity, suggesting that another f actor(s), such as tumour-produced cytokines, influences LC density, It has been postulated that dendritic epidermal T cells (DETCs) play a r ole in immunosurveillance within the normal epidermis, Two cytokines w hich potentially alter LC numbers or function include granulocyte-macr ophage colony-stimulating factor (GM-CSF) and tumour necrosis factor-a lpha (TNF-alpha). GM-CSF maintains LC viability in culture, and there are reports that it can increase LC density, There is evidence that TN F-alpha induces LC to migrate from the epidermis, In the present study , LC densities in regressor and non-regressor murine skin tumours and overlying epidermis were enumerated, and bioactive GM-CSF and TNF-alph a present in the tumours were measured, We found significantly increas ed epidermal LC numbers above non regressor, but not regressor, tumour s. DETC numbers were significantly increased above some tumours, Altho ugh all tumour types produced TNF-alpha, the regressors, which did not increase LC numbers, produced the most TNF-alpha. In contrast, tumour production of GM-CSF did not correlate with any pattern of alteration of LC density or tumour growth. Tumour production of neither cytokine nor tumour growth correlated with DETC numbers overlying tumours, Our results suggest that TNF-alpha may be associated with skin tumour reg ression and may prevent LC accumulation by tumours. (C) 1998 Wiley-Lis s, Inc.