Recent early phase clinical trials have shown impressive activity of the anti-PD1 monoclonal antibodies nivolumab and pembrolizumab in metastatic melanoma, irrespective of BRAF mutation status. (1,2). ‘Immune-evasion’ therapies targeting the rate-limiting enzyme of the tryptophan catabolizing pathway indoleamine 2,3-dioxygenase (IDO1) also show pre-clinical activity against melanoma (3). However, biomarkers of immune-escape in melanoma pre- and post-therapy are still clinically required. We have undertaken studies to identify potential immune-evasion targets and biomarker expression in advanced melanoma. Patient derived melanoma cell-lines were established from four different biopsy lesions obtained pre-therapy, post-therapy and following resistance to an approximate 6-month duration of combined dabrafenib and trametinib therapy. The cell-lines were treated with interferon (IFN)-γ (100U) alone or in combination with 100nM dabrafenib and 10nM trametinib for 24 to 72h. High performance liquid chromatography, immunoblot and cytokine studies were performed. Statistical analysis was performed using one-way ANOVA (p<0.05). IFN-γ induced tryptophan metabolism was significantly enhanced in all cells at 24h (p<0.001), and this was either absent or significantly reduced following co-treatment with dabrafenib and trametinib (p<0.05). Immunoblot analysis demonstrated that IDO1 steady-state protein expression was positively correlated with tryptophan metabolism. We observed an increase in PD-L1 steady-state protein levels following IFN-γ treatment which was partially reduced or reversed following co-treatment with dabrafenib and trametinib. Cytokine production of GROα/CXCL1, SICAM-1/CD54, IL8/CXCL8, MIF/GIF/DER6 and Serpin E1/PAI-1 were identified in all control treated cell-lines. Furthermore, IFN-γ treatment induced IFNγ/Type II IFN and IP10/CKCL11 cytokine expression. Interestingly, the cytokines IL6, MCP-1/CCL2, SDF-1/CXCL12, sTREM-1 and C5/C5a were uniquely IFN-γ stimulated in post-therapy and therapy-resistant cell-lines. These findings suggest that, PD-L1 and IDO1 combinatorial immune-evasion therapies are of potential value for advanced melanoma. Future studies investigating the role of IL6, MCP-1/CCL2, SDF-1/CXCL12, sTREM-1 and C5/C5a in advanced melanoma as potential biomarkers of immune-evasion are warranted.