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. Cutaneous squamous cell carcinoma (SCC) is the most common cancer with the potential to threaten life if left untreated. The “gold standard” treatment for SCC is surgical removal, however, this does not instigate a means to prevent tumour recurrence, and patients with one SCC show an increased incidence of secondary SCC’s. Due to the mutagenic effects of UV light, SCC carry a high mutational load and are considered to be highly immunogenic, and therefore immunotherapy holds promise for the induction of long-term protective immunity. To study the immune mechanisms important for the regression of SCC, we have created a mouse SCC cell line derived from UV-irradiated HPV38 E6/E7 FVB mice. This cell line forms tumours when injected into immune suppressed mice, which subsequently regress following the removal of immunosuppression. Preliminary data utilizing neutralizing and blocking antibodies show that IFN-g and CXCR3, respectively, are both critical for the regression of SCC. Neutralizing IFN-g in vivo through treatment with anti-IFN-g, impaired CD8+ T-cell infiltration into the tumour site, and resulted in uncontrolled tumour growth. Blockade of CXCR3 in vivo through treatment with anti-CXCR3, also reduced the number of CD8+ T-cells infiltrating into tumours, and delayed tumour regression. Importantly, the number of CD8+ T-cells within the tumour was found to positively correlate with the degree of SCC regression. Together, the data strongly suggest a key role for IFN-g and CXCR3 in the CD8+ T-cell-mediated control of SCC regression.