PRF1 and neoplasm: In this context, two main mechanisms are responsible for NK cell-mediated cytotoxicity resistance: 1) tumor cells take advantage of co-inhibitory signaling to avoid NK cell-mediated responses, leading this immune subset to an anergic or irresponsiveness state, and 2) tumor cells avoid NK cell effector activity after target cell recognition (i.e., inefficient perforin (PRF1) binding).