Cutting edge: granzymes A and B are not essential for perforin-mediated tumor rejection.
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.
Smyth
Mark J
MJ
Cancer Immunology Program, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia. m.smyth@pmci.unimelb.edu.au
Street
Shayna E A
SE
Trapani
Joseph A
JA
D000818:Animals; D018827:Carcinoma, Lewis Lung; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D006084:Graft Rejection / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D053804:Granzymes; D018664:Interleukin-12 / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D007694:Killer Cells, Natural / Q000201:enzymology / Q000276:immunology; D008223:Lymphoma / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D008546:Melanoma, Experimental / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D018664:Interleukin-12; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases