Organ transplant recipients have an increased risk of non-melanoma skin cancer development. Immunosuppressive agents, given to these patients to prevent organ rejection, are widely recognised to play a key role in the increased incidence of malignancy. However, different immunosuppressive agents, such as rapamycin and tacrolimus, which both prevent organ rejection, appear to convey different risks of tumour formation. Using a UV-induced murine model of squamous cell carcinoma (SCC); HPV38 E6E7, we hope to determine whether these differences are due to a direct influence of these drugs on tumour cells, or an indirect influence mediated via differences in mechanisms of immune suppression. When added to mice diet at a concentration of 20mg/kg over 8 weeks, rapamycin did not result in any gross health problems. A steady state concentration of 3-4ng/ml of rapamycin in the blood could be detected by LC-MS/MS analysis; however adoptively transferred transgenic T-cell proliferation and the rate of allogenic skin graft rejection appeared unaffected in these mice. We will shortly begin testing the addition of 100mg/kg of rapamycin in the diet to see whether we can reach the immunosuppressive threshold, which in humans is 15-20ng/ml. We will also begin work to establish optimal UV dosing schedules for SCC development. Through this project, we hope to expand our knowledge base regarding mechanisms of SCC formation in immunosuppressed patients.