Ability of cyclosporine to promote the growth of transplanted ultraviolet radiation-induced tumors in mice.

The use of immunosuppressive agents (primarily azathioprine and prednisone) to promote human allograft survival is known to be associated with an enhanced rate of skin cancer development by ultraviolet radiation (UVR). These observations raise the question of whether the immunosuppressive agents are functioning as cocarcinogen or whether they augment UVR-induced tumors by their successive influence on normal tumor-directed immune responses. In this report we have examined the effect of cyclosporine (CsA) on the capacity of murine UVR-induced tumors to grow following their transplantation to syngeneic recipients. We found that transplanted UVR tumors, selected for their inability to grow in normal recipients, were capable of progressive growth following implantation into CsA-treated recipients. This CsA-induced tumor-susceptible state could be reversed by treatment of prospective recipients with the drug cyclophosphamide (CY), supporting the concept that CsA was functioning in vivo by its capacity to promote suppressor cell generation. Further studies established that CsA treatment needed to be given at or near the time of tumor transplantation for susceptibility to occur. Our findings support the possibility that CsA is capable of promoting the survival and progression of UVR-induced skin tumors via its capacity to enhance the dominance of suppressor-cell-controlled immune responses.