Perforin-dependent cytotoxicity: 'Kiss of death' or prolonged embrace with darker consequences?

Abstract

Failure of natural killer (NK) cells or cytotoxic T-lymphocytes (CTL) to kill cognate target cells results in cytokine/chemokine hypersecretion and markedly delayed killer/target cell detachment. With congenital perforin deficiency, fatal cytokine storm results. In cancer cells, where corrupted apoptotic signaling frequently delays apoptosis, we propose that failed death may alter the tumor microenvironment and skew immune infiltrates, even when perforin is delivered normally.