Merkel cell carcinomas are highly immunogenic neuroendocrine skin cancers with two distinct aetiologies – one associated with the Merkel cell polyoma virus (MCPyV) and the other with UV-carcinogenesis. While multiple MCC cell lines have been previously described, most represent viral-positive MCC (VP-MCC). We established four MCC cell lines: three VN-MCC and one VP-MCC. Two cell lines were established from patient derived xenografts and two directly from tumour explants. All cell lines display a classical non-adherent growth pattern in culture and whole genome sequencing showed matching mutational profiles in cell lines and originating tumours. High tumour mutation burden, a UV-mutation signature, RB1 and TP53 mutations were all detected in VN-MCC, while the VP-MCC cell line had MCPyV genome integration and a UV signature with low mutation burden, which was a novel observation in VP-MCC. The cell lines differentially expressed neuroendocrine and epithelial to mesenchymal transition (EMT) marker genes. Type II interferon (IFNg) treatment of the four cell lines revealed two distinct transcriptional responses (sig-A and sig-B). Gene-expression correlates of sig-A in a series of bulk tissue RNA analysed MCC tumours showed correlation to T cell markers, consistent with the sig-A expressing cell lines originating from tumours with brisk T cell (CD8+ and gdT+) infiltrates and high PD-L1 expression. Sig-B correlated to myeloid cell gene markers and cell lines originated from tumours with low T cell infiltrates. Gene set enrichment analysis testing sig-A and sig-B combined with Cox-regression survival analysis in an expanded patient cohort (n=89) showed better overall survival for those patients with high sig-A enrichment scores (>75th percentile, p=0.003). We therefore demonstrated our MCC cell lines are representative models of VN and VP-MCC and that immune response and patient survival may be associated with an intrinsic cellular program linked to IFNg response in tumour cells.