The method recapitulated tumour microenvironmental stresses, e.g. nutrient deprivation, pH changes and waste product accumulation, created as a gradient from the lumen, that enhanced ‘exhaustion-like’ features in NK cells analogous to those of T cells, e.g. upregulation of PD-1 and reduced expression of TNF-α. This evidence concerns the gene PDCD1 and neoplasm.