Factors associated with the induction of ‘exhaustion’ in CD8+ T cells and NK cells within the tumour microenvironment, include the AhR, TGF-β, CD73 (ecto-5-Nucleotidase), adenosine A2Ar activation, PD-1, and the COX2/PGE2/EP4 pathway. This evidence concerns the gene PDCD1 and neoplasm.