Australia has the highest incidence of skin cancer in the world, causing considerable social and economic burden. Indeed, two out of every three Australians are likely to be diagnosed with skin cancer by the age of 70. Compared to the general population, organ transplant recipients experience a 60-100 fold increased risk of squamous cell carcinoma development due to impaired immune surveillance as a consequence of their lifelong regime of prescribed immunosuppressive drugs, such as Tacrolimus. However, a decreased incidence of de novo squamous cell carcinoma development is reported in patients treated with the mammalian target of rapamycin (mTOR) inhibitor Rapamycin (Sirolimus). Unfortunately, Sirolimus is associated with an array of unpleasant side effects, and consequently many patients discontinue treatment. At present, the mechanism behind Rapamycin’s antineoplastic effects are unknown. As reports suggest Rapamycin may promote the development of memory CD8 T-cells in the skin, we aimed to investigate the involvement of CD8 T-cells in Rapamycin’s effects on tumour progression. Preliminary data showed that in T-cell deficient Rag1-/- mice, Rapamycin treatment prevented the establishment of tumours, suggesting T and B cells were not required for Rapamycin-mediated prevention of de novo tumour formation. However, the transfer of T-cells from Rapamycin-treated mice to Rag 1-/- mice with established squamous cell carcinomas induced a reduction in tumour growth suggesting that Rapamycin may allow the priming of anti-tumour CD8 T-cells in the skin. We are currently optimising a multiplex method of immunohistochemistry to examine immune subpopulations within tumours. Preliminary studies investigating CD3 and CD8 co-localisation suggested greater T-cell infiltration into a regressing tumour under Rapamycin treatment. A more in depth understanding of the tumour microenvironment between growing, static and regressing tumours will help to elucidate the effects of Rapamycin on the immune response.