Besides the expression of immune checkpoint molecules on tumor cells, the presence of an immunologically “hot” TME, infiltrated by cytotoxic T cells, and the tumor mutational burden (TMB) that provides adaptive immunity with neo-antigen targets against which a robust cell-mediated response can arise, are also pre-requisites for the effectiveness of anti-PD-1/PD-L1 therapeutic targeting. This evidence concerns the gene PDCD1 and neoplasm.