Transforming growth factor-β1 immobilises dendritic cells within skin tumours and facilitates tumour escape from the immune system

Human skin tumours often regress spontaneously due to immune rejection. Murine skin tumours model this behaviour; some regress and others progress in syngeneic immunocompetent hosts. Previous studies have shown that progressor but not regressor skin tumours inhibit dendritic cell ( DC) migration from the tumour to draining lymph nodes, and transforming growth factor-beta(1) (TGF-beta(1)) has been identified as a responsible factor. To determine whether increased production of TGF-beta(1) in the absence of other differences inhibits DC migration from the tumour and enables it to evade immune destruction, a murine regressor squamous cell carcinoma clone was transfected with the gene for TGF-beta(1). This enhanced growth in vitro and in vivo, causing it to become a progressor. TGF-beta(1) transfection reduced the number of infiltrating DCs by about 25%. Quantitation of CD11c(+) E-cadherin(+) (epidermally derived) DCs in lymph nodes determined that TGF-beta(1) reduced the number of DCs that migrated from the tumour to undetectable levels. This was supported by showing that TGF-beta(1) reduced DC migration from cultured tumour explants by greater than tenfold. TGF-beta(1) transfection also reduced the number of infiltrating CD4 and CD8 T cells. Thus, TGF-beta(1) production by skin tumours is sufficient to immobilise DCs within the tumour, preventing their migration to lymph nodes. This reduces the number of T cells that infiltrate the tumour, preventing regression. Thus, TGF-beta(1) is a key regulator of whether skin tumours regress or progress.