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Robert van Domselaar

Monday 19 March 2012

Antiviral and anticancer functions of granzymes

Promotor: Prof. dr. van Diest
Defence: 5 June 2012
Summary
Cytotoxic lymphocytes are the key effector immune cells that deal with tumor cells and virus-infected cells. The granule-exocytosis pathway is the most 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 (GrA, GrB, GrH, GrK, and GrM) 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 described new granzyme functions, which were identified by studying novel granzyme substrates and their role in the induction of apoptosis or inhibition of viral replication.Back