Antiviral and anticancer functions of granzymes

Abstract

Cytotoxic lymphocytes are the key effector immune cells that deal with tumor cells and virus-infected cells. The granule-exocytosis pathway is an important pathway by which cytotoxic lymphocytes exert their antiviral and anticancer functions. Activated cytotoxic lymphocytes release granules, containing a family of homologues serine proteases called granzymes, and the membrane-perturbing protein perforin that facilitates the entry of granzymes into the target cell. Although it has been demonstrated that all five human granzymes can induce cell death through distinct pathways, they do not solely induce target cell death. Novel roles for granzymes are emerging, including induction of cytokine responses and inhibition of viral replication independent of cell death. My thesis describes new granzyme functions, which were identified by studying novel granzyme substrates and their role in the induction of apoptosis in tumor cells or inhibition of viral replication.