In head and neck squamous cell carcinoma, adenosinergic signalling (via CD39/CD73 and the A2A receptor) is germane to perineural compartments; in human specimens this can be assayed by multiplex IHC (CD39, CD73, A2A with CD8/FOXP3) (47), RNA-ISH for NT5E/ENTPD1, spatial metabolomics for adenosine/ATP ratios, and ex vivo A2A-pharmacodynamic readouts (pCREB in T cells) (48). Here, NT5E is linked to head and neck squamous cell carcinoma.