This advanced disease model is more akin to metastatic human tumours, and is considerably more immunosuppressive with heavier tumour burden (Supplementary Fig. 8a–c) and increased immunosuppressive factor expression in the tumour microenvironment (PD-1, PD-L1, CTLA-4, TGF-β, CD105, and VEGF, Supplementary Fig. 8d). This evidence concerns the gene CTLA4 and neoplasm.