There are two case reports describing responses to immunotherapy in patients with CUP; one patient with high expression levels of programmed cell death ligand-1 (PDL1), and the other had confirmed dMMR (Supplementary Table S1).66,68 Recently published works have demonstrated the efficacy of pembrolizumab in dMMR and MSI-high tumours irrespective of tumour cell origin;71,72 consequently, pembrolizumab is the first drug to gain pan-cancer FDA approval for use in any MSI-high/dMMR solid tumour. This evidence concerns the gene CD274 and neoplasm.