Cutaneous melanoma is a lethal form of skin cancer that accounts for 9th most common cause of cancer-related deaths in Australia. The current standard of care for BRAF mutant melanoma is a combination of BRAF and MEK inhibitors (BRAFi/MEKi). However, despite the remarkable initial response rate, most patients relapse after acquiring resistance. Therefore, novel therapeutic strategies are necessary. Pre-clinical studies from our lab have demonstrated PRMT5 inhibitors as single agents or in combination with CDK4/6 inhibitors are an effective therapeutic strategy for melanoma. Targeted therapies have both tumour intrinsic responses but also can impact on the immune system affecting anti-tumour immunity. Thus, we hypothesis that PRMT5 inhibition will also impact on immune-mediated anti-tumour immune responses. Here, we investigate the immunomodulatory effects of PRMT5 inhibition (PRTM5i) using the immunogenic YOVAL1.1 mouse model and isolated CD8+ T-cells. Flow cytometry analyses of immune markers on the tumour cells revealed an upregulation of the co-stimulatory molecule CD80 and downregulation of MHC class I expression. More importantly, chromium T-cell killing assays illustrated, an increase in T-cell mediate killing when co-cultured with treated tumour cells with PRMT5i. In addition, PRTM5i treatment of CD8+ T-cells showed negligible modulation in T-cell activation marker, phenotype and viability. Overall, results from this study support the immunomodulatory effects of PRMT5i, which can potentially increase the anti-melanoma immune response.