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The Journal of Immunology, 2003, 171: 515-518.
Copyright © 2003 by The American Association of Immunologists


CUTTING EDGE

Cutting Edge: Granzymes A and B Are Not Essential for Perforin-Mediated Tumor Rejection

Mark J. Smyth, Shayna E. A. Street and Joseph A. Trapani

Cancer Immunology Program, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia

Controversy still exists regarding the biological function of granzyme serine proteases released with perforin from the cytotoxic granules of NK cells and CTLs. In particular, it is not clear whether the major granzymes, A and B, play an essential role in tumor rejection mediated by the perforin pathway. We have now examined the relative importance of perforin and granzyme A and B clusters in five different tumor models that stringently distinguish their importance. We conclude that granzyme A and B clusters are not essential for CTL- and NK cell-mediated rejection of spontaneous and experimental tumors, raising the likelihood that either perforin alone or in combination with an additional granzyme or granule component(s) mediates cytotoxicity of tumor cells in vivo.




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