Progressor but not regressor skin tumours inhibit Langerhans' cell migration from epidermis to local lymph nodes.
Langerhans' cells (LC) are found in high numbers infiltrating skin tumours, the functional significance of which remains unknown. To study the mechanism by which tumours increase the number of LC we developed a procedure whereby supernatant from cultured T7 tumour cells applied topically increases the number of LC. Tumour factors increased the number of resident epidermal LC and did not attract LC precursors into parental murine skin grafted onto F1 hybrids. There was no evidence for increased LC division in response to the tumour-derived factors. LC migration from the epidermis to local lymph nodes, induced by topical fluorescein isothiocyanate (FITC), was inhibited by the tumour supernatant. To examine the functional significance of this, FITC-induced migration of LC from the epidermis overlying progressor tumours, which evade immunological destruction, and regressor tumours, which are immunologically destroyed, was examined. The progressor tumour T7 growing subcutaneously in syngeneic mice inhibited FITC-induced migration of LC from overlying epidermis. Furthermore, two progressor, but not two regressor murine skin tumour lines growing in BALB/c nu/nu mice inhibited LC migration from the epidermis. Our results demonstrate that progressor skin tumours produce factor(s) which inhibit LC migration from the epidermis to lymph nodes, leading to LC accumulation. Inhibition of LC migration by tumour-derived factors may enable tumours to evade the activation of protective immunity as regressor tumours do not interfere with the normal trafficking of LC.
Lucas
A D
AD
Department of Medicine (Dermatology), University of Sydney at Royal Prince Alfred Hospital, Sydney, Australia.
Halliday
G M
GM
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D004817:Epidermis / Q000276:immunology*; D005260:Female; D007801:Langerhans Cells / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured