The PD-1 ability to inhibit the initiation of both the TCR and CD28 signaling pathways explains the pleiotropic functional outcomes that result from its engagement (Sharpe and Pauken, 2018) and accounts for the ability of PD-1 to suppress TILs directed against non-hematopoietic tumor cells that express ligands of PD-1 but not those of CD28. Here, PDCD1 is linked to neoplasm.