Here we propose that factors such as tumour-intrinsic IC signalling, the impact of pH in the tumour microenvironment on mAb functionality, gut and tumour microbiome composition, patients race and endocrine status, ICs and FcRs polymorphisms and the impact of PD-1/PD-L1 blockade on the PD-1 interaction with its other ligand/s deserve attention in the process of elucidating HP mechanisms. The gene discussed is PDCD1; the disease is neoplasm.