Cutaneous squamous cell carcinoma (cSCC) is one of the most prevalent cancers in Caucasian populations, and its aggressive form poses a high risk of metastasis resulting in increased rates of mortality and morbidity. Recurrent and chronic exposure to ultraviolet (UV) radiation from the sun plays a crucial role in the initiation, development, and perpetuation of cSCC. Accumulating evidence suggests that regulatory T (Treg) cells are associated with UV-induced immunosuppression, however, their direct contribution to the establishment of cSCC remains elusive. When mice were exposed to 5 consecutive days of UVB (dose rate 150mJ/cm2), they showed reduced ear swelling in response to ovalbumin challenge in a contact hypersensitivity assay, suggesting that functional antigen specific Tregs were induced. However, ear swelling responses did not show signs of suppression when mice were treated with anti-CTLA-4 and anti-TIGIT antibodies following the cessation of UV treatment. Phenotypically, the expression of Foxp3, FR4, CTLA-4 and TIGIT on Tregs in the inguinal lymph nodes and spleen of UV-exposed mice did not differ from those in non-UV-exposed mice. Following the treatment of mice with UVB 5 days per week for different time periods (2w, 4w, 6w, 8w), it was determined that only UVB treatment for eight weeks consistently allowed the establishment and growth of tumours following the adoptive transfer of cSCC tumour fragments from donor mice. We aim to target Tregs in these tumour models in our future studies to determine whether Treg depletion or manipulation will reverse the capacity of UV to enable cSCC tumour establishment. Overall, this study will examine the plausibility of Treg manipulation as a preventative strategy to prevent UV-induced cSCC tumour establishment.