Journal article

Perforin and granzymes: function, dysfunction and human pathology

Ilia Voskoboinik, James C Whisstock, Joseph A Trapani



A defining property of cytotoxic lymphocytes is their expression and regulated secretion of potent toxins, including the pore-forming protein perforin and serine protease granzymes. Until recently, mechanisms of pore formation and granzyme transfer into the target cell were poorly understood, but advances in structural and cellular biology have now begun to unravel how synergy between perforin and granzymes brings about target cell death. These and other advances are demonstrating the surprisingly broad pathophysiological roles of the perforin–granzyme pathway, and this has important implications for understanding immune homeostasis and for developing immunotherapies for cancer and other dis..

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Funding Acknowledgements

I.V. and J.C.W. are supported by fellowships from the National Health and Medical Research Council of Australia (NHMRC). I.V., J.C.W. and J.A.T. are supported by project grants from the NHMRC. J.C.W. is supported by the Australian Research Council (ARC) and he acknowledges the support of an ARC Federation fellowship. J.A.T. is supported by a programme grant from the NHMRC. The authors thank the many members of their laboratories, especially J.A. Lopez and A.J. Brennan, and their collaborators, especially H. Saibil, M.A. Dunstone, R. H. P. Law and N. Lukoyanova, for their contributions to many of the findings discussed in this Review.