J A Trapani

Summary

Affiliation: University of Melbourne
Country: Australia

Publications

  1. ncbi request reprint Tumor-mediated apoptosis of cancer-specific T lymphocytes--reversing the "kiss of death"?
    Joseph A Trapani
    Cancer Immunology Program, Peter MacCallum Cancer Institute, A Beckett Street, 8006, Melbourne, Australia
    Cancer Cell 2:169-71. 2002
  2. pmc Granzymes: a family of lymphocyte granule serine proteases
    J A Trapani
    Cancer Immunology Division, Trescowthick Laboratories, Peter MacCallum Cancer Institute, Locked Bag 1, A Beckett St, 8006, Melbourne, Australia
    Genome Biol 2:REVIEWS3014. 2001
  3. ncbi request reprint Functional significance of the perforin/granzyme cell death pathway
    Joseph A Trapani
    Cancer Immunology Laboratory, Trescowthick Research Laboratories, Research Division, Peter MacCallum Cancer Institute, Locked Bag 1, A Beckett Street, Melbourne 8006, Australia
    Nat Rev Immunol 2:735-47. 2002
  4. pmc A clathrin/dynamin- and mannose-6-phosphate receptor-independent pathway for granzyme B-induced cell death
    Joseph A Trapani
    Cancer Immunology Laboratory, Peter MacCallum Cancer Institute, Melbourne 8006, Australia
    J Cell Biol 160:223-33. 2003
  5. ncbi request reprint Granzyme B: pro-apoptotic, antiviral and antitumor functions
    Joseph A Trapani
    Cancer Immunology Program, Research Division, Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett Street, Melbourne 8006, Australia
    Curr Opin Immunol 15:533-43. 2003
  6. doi request reprint Blocking granule-mediated death by primary human NK cells requires both protection of mitochondria and inhibition of caspase activity
    K A Sedelies
    Cancer Cell Death Laboratory, Cancer Immunology Program, Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett Street, Melbourne, Victoria 8006, Australia
    Cell Death Differ 15:708-17. 2008
  7. ncbi request reprint Functional dissociation of DeltaPsim and cytochrome c release defines the contribution of mitochondria upstream of caspase activation during granzyme B-induced apoptosis
    N J Waterhouse
    Cancer Cell Death, Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett Street, Melbourne, Victoria 8006, Australia
    Cell Death Differ 13:607-18. 2006
  8. pmc Initiation of apoptosis by granzyme B requires direct cleavage of bid, but not direct granzyme B-mediated caspase activation
    V R Sutton
    Cancer Immunology Laboratory, Peter MacCallum Cancer Institute, Melbourne 8006, Australia
    J Exp Med 192:1403-14. 2000
  9. ncbi request reprint Critical role of the transcription factor AP-1 for the constitutive and interferon-induced expression of IFI 16
    C J P Clarke
    Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, Victoria 3002, Australia
    J Cell Biochem 89:80-93. 2003
  10. pmc Granzyme B triggers a prolonged pressure to die in Bcl-2 overexpressing cells, defining a window of opportunity for effective treatment with ABT-737
    V R Sutton
    Cancer Cell Death Laboratory, Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria 8006, Australia
    Cell Death Dis 3:e344. 2012

Collaborators

Detail Information

Publications86

  1. ncbi request reprint Tumor-mediated apoptosis of cancer-specific T lymphocytes--reversing the "kiss of death"?
    Joseph A Trapani
    Cancer Immunology Program, Peter MacCallum Cancer Institute, A Beckett Street, 8006, Melbourne, Australia
    Cancer Cell 2:169-71. 2002
    ..Several other potential tumor escape mechanisms that can block the cytotoxic pathways activated by killer T cells have also been proposed...
  2. pmc Granzymes: a family of lymphocyte granule serine proteases
    J A Trapani
    Cancer Immunology Division, Trescowthick Laboratories, Peter MacCallum Cancer Institute, Locked Bag 1, A Beckett St, 8006, Melbourne, Australia
    Genome Biol 2:REVIEWS3014. 2001
    ..Future studies of serpins may bring insights into how cells that synthesize granzymes are protected from inadvertent cell suicide...
  3. ncbi request reprint Functional significance of the perforin/granzyme cell death pathway
    Joseph A Trapani
    Cancer Immunology Laboratory, Trescowthick Research Laboratories, Research Division, Peter MacCallum Cancer Institute, Locked Bag 1, A Beckett Street, Melbourne 8006, Australia
    Nat Rev Immunol 2:735-47. 2002
    ....
  4. pmc A clathrin/dynamin- and mannose-6-phosphate receptor-independent pathway for granzyme B-induced cell death
    Joseph A Trapani
    Cancer Immunology Laboratory, Peter MacCallum Cancer Institute, Melbourne 8006, Australia
    J Cell Biol 160:223-33. 2003
    ..Entry of granzyme B into target cells and its intracellular trafficking to induce target cell death in the presence of perforin are therefore not critically dependent on MPR or clathrin/dynamin-dependent endocytosis...
  5. ncbi request reprint Granzyme B: pro-apoptotic, antiviral and antitumor functions
    Joseph A Trapani
    Cancer Immunology Program, Research Division, Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett Street, Melbourne 8006, Australia
    Curr Opin Immunol 15:533-43. 2003
    ..The recent discovery of a triply mutated human granzyme B allele, whose product is predicted to possess a reduced capacity to induce cell death, opens the way for major progress in these areas in coming years...
  6. doi request reprint Blocking granule-mediated death by primary human NK cells requires both protection of mitochondria and inhibition of caspase activity
    K A Sedelies
    Cancer Cell Death Laboratory, Cancer Immunology Program, Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett Street, Melbourne, Victoria 8006, Australia
    Cell Death Differ 15:708-17. 2008
    ....
  7. ncbi request reprint Functional dissociation of DeltaPsim and cytochrome c release defines the contribution of mitochondria upstream of caspase activation during granzyme B-induced apoptosis
    N J Waterhouse
    Cancer Cell Death, Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett Street, Melbourne, Victoria 8006, Australia
    Cell Death Differ 13:607-18. 2006
    ..This functional dissociation of cytochrome c and SMAC release from loss of DeltaPsim demonstrates the essential contribution of Bid upstream of caspase activation during granzyme B-induced apoptosis...
  8. pmc Initiation of apoptosis by granzyme B requires direct cleavage of bid, but not direct granzyme B-mediated caspase activation
    V R Sutton
    Cancer Immunology Laboratory, Peter MacCallum Cancer Institute, Melbourne 8006, Australia
    J Exp Med 192:1403-14. 2000
    ..Overall, our results indicate that mitochondrial perturbation by Bid is necessary to achieve a lethal threshold of caspase activity and cell death due to granzyme B...
  9. ncbi request reprint Critical role of the transcription factor AP-1 for the constitutive and interferon-induced expression of IFI 16
    C J P Clarke
    Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, Victoria 3002, Australia
    J Cell Biochem 89:80-93. 2003
    ..These experiments define the transcriptional mechanisms of IFI 16 gene regulation and provide evidence suggesting that AP-1 activation may be an important event in IFN signaling...
  10. pmc Granzyme B triggers a prolonged pressure to die in Bcl-2 overexpressing cells, defining a window of opportunity for effective treatment with ABT-737
    V R Sutton
    Cancer Cell Death Laboratory, Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria 8006, Australia
    Cell Death Dis 3:e344. 2012
    ..This defines a therapeutic window in which ABT-737 and CL synergise to cause maximum death of cancer cells that are resistant to either treatment alone, which will be essential in defining optimum treatment regimens...
  11. doi request reprint Gene-modified T cells as immunotherapy for multiple myeloma and acute myeloid leukemia expressing the Lewis Y antigen
    S Peinert
    Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Victoria, Australia
    Gene Ther 17:678-86. 2010
    ..Consequently, we plan to use T cells manufactured under Good Manufacturing Practice conditions in a phase I immunotherapy study for patients with Le(Y)-positive myeloma or AML...
  12. doi request reprint Ex vivo culture of chimeric antigen receptor T cells generates functional CD8+ T cells with effector and central memory-like phenotype
    P Neeson
    Hematology and Immunology Translational Research Lab, Peter MacCallum Cancer Center, Melbourne, Australia
    Gene Ther 17:1105-16. 2010
    ..This study confirms CD8(+) LeY-T cells have a CM- and EM-like phenotype and heterogeneous function consistent with potential to persist in vivo after adoptive transfer...
  13. ncbi request reprint CTL: Caspases Terminate Life, but that's not the whole story
    N J Waterhouse
    Cancer Immunology Laboratory, Research Division, Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, Australia
    Tissue Antigens 59:175-83. 2002
    ..Here we will discuss the mechanisms by which these stellar killers achieve their goal...
  14. ncbi request reprint Unlocking the secrets of cytotoxic granule proteins
    M J Smyth
    Cancer Immunology Division, Trescowthick Laboratories, Peter MacCallum Cancer Institute, Melbourne, Australia
    J Leukoc Biol 70:18-29. 2001
    ....
  15. pmc Mouse granzyme A induces a novel death with writhing morphology that is mechanistically distinct from granzyme B-induced apoptosis
    O Susanto
    1 Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia 2 Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia
    Cell Death Differ 20:1183-93. 2013
    ..This work defines an authentic role for mouse Gzm A in granule-induced cell death by cytotoxic lymphocytes. ..
  16. ncbi request reprint Filamin (280-kDa actin-binding protein) is a caspase substrate and is also cleaved directly by the cytotoxic T lymphocyte protease granzyme B during apoptosis
    K A Browne
    Cancer Immunology Laboratory, Peter MacCallum Cancer Institute, Locked Bag 1, A Beckett Street, Melbourne 8006, Australia
    J Biol Chem 275:39262-6. 2000
    ..Thus, filamin is a functionally important substrate for granzyme B, as its cleavage may account at least partly for caspase-independent cell death mediated by the granzyme...
  17. ncbi request reprint Functional interaction between p53 and the interferon-inducible nucleoprotein IFI 16
    R W Johnstone
    The Peter MacCallum Cancer Institute, Cancer Immunology Division, East Melbourne, Victoria, Australia
    Oncogene 19:6033-42. 2000
    ..These findings demonstrate a possible link between gene induction following interferon stimulation and p53-mediated cellular events...
  18. ncbi request reprint Mechanisms of interferon mediated anti-viral resistance
    C J Clarke
    Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, Victoria 3002, Australia
    Curr Drug Targets Immune Endocr Metabol Disord 1:117-30. 2001
    ..This review explains the current model of IFN action, during viral infections and the potential for well-established and emerging groups of IFN inducible genes as therapeutic targets is highlighted...
  19. ncbi request reprint Isotypic variants of the interferon-inducible transcriptional repressor IFI 16 arise through differential mRNA splicing
    R W Johnstone
    The John Connell Laboratory, The Austin Research Institute, Heidelberg, Australia
    Biochemistry 37:11924-31. 1998
    ..Finally, IFI 16 isoforms can homo- and heterodimerize, and we have mapped the dimerization domain to the amino terminus which contains an imperfect leucine zipper domain...
  20. ncbi request reprint Anti-viral strategies of cytotoxic T lymphocytes are manifested through a variety of granule-bound pathways of apoptosis induction
    K M Edwards
    John Connell Laboratory, Austin Research Institute, Heidelberg, Victoria, Australia
    Immunol Cell Biol 77:76-89. 1999
    ..The fate of such a cell therefore reflects the balance of pro-apoptotic (immune) and anti-apoptotic (viral) strategies that have developed over eons of evolutionary time...
  21. ncbi request reprint The human interferon-inducible protein, IFI 16, is a repressor of transcription
    R W Johnstone
    The Austin Research Institute, Austin Hospital, Studley Road, Heidelberg 3084, Victoria, Australia
    J Biol Chem 273:17172-7. 1998
    ..Thus, IFI 16 is a transcriptional repressor, with a modular structure typical of many known transcription regulators...
  22. ncbi request reprint Perforin-dependent nuclear entry of granzyme B precedes apoptosis, and is not a consequence of nuclear membrane dysfunction
    J A Trapani
    Cellular Cytotoxicity Laboratory, The Austin Research Institute, Studley Road, Heidelberg, 3084, Australia
    Cell Death Differ 5:488-96. 1998
    ..Rather, a perforin-dependent signal results in a redistribution of grB from the cytoplasm to the nucleus, where it may contribute to the nuclear changes associated with apoptosis...
  23. ncbi request reprint Efficient nuclear targeting of granzyme B and the nuclear consequences of apoptosis induced by granzyme B and perforin are caspase-dependent, but cell death is caspase-independent
    J A Trapani
    The John Connell Laboratory, The Austin Research Institute, Studley Road, Heidelberg 3084, Australia
    J Biol Chem 273:27934-8. 1998
    ..We conclude that cell death in response to perforin and granzyme B does not require caspase activation and still proceeds efficiently through non-nuclear pathways when nuclear substrate cleavage is inhibited...
  24. ncbi request reprint Redirected perforin-dependent lysis of colon carcinoma by ex vivo genetically engineered CTL
    P K Darcy
    Cellular Cytotoxicity Laboratory, The Austin Research Institute, Heidelberg, Victoria, Australia
    J Immunol 164:3705-12. 2000
    ..This series of experiments has revealed the utility of scFv anti-CEA chimeras in providing mouse T cells the capacity to reject colon carcinoma in an Ag- and perforin-specific manner...
  25. ncbi request reprint CTL granules: evolution of vesicles essential for combating virus infections
    J A Trapani
    Austin Research Institute, Studley Road, Heidelberg 3084, Australia
    Immunol Today 20:351-6. 1999
    ..Here, Joseph Trapani and colleagues argue that CTL cytolytic granules are the principal apoptotic means of eliminating viruses and possess multiple independent mechanisms to counter the viral anti-apoptotic machinery...
  26. ncbi request reprint Adoptive transfer: the role of perforin in mouse cytotoxic T lymphocyte rejection of human tumor xenografts in vivo
    M J Smyth
    Cellular Cytotoxicity Laboratory, The Austin Research Institute, Heidelberg, Victoria, Australia
    Xenotransplantation 5:146-53. 1998
    ..These data indicate that perforin, and hence direct cytotoxicity, plays a key role in the ability of adoptively transferred CD8+ cytotoxic T lymphocytes to eradicate established xenografts...
  27. pmc Differential tumor surveillance by natural killer (NK) and NKT cells
    M J Smyth
    Cellular Cytotoxicity Laboratory, Austin Research Institute, Austin and Repatriation Medical Centre, Heidelberg, 3084 Victoria, Australia
    J Exp Med 191:661-8. 2000
    ..This is the first description of an antitumor function for NKT cells in the absence of exogenously administered potent stimulators such as IL-12 or alpha-galactosylceramide...
  28. doi request reprint Controversies in granzyme biology
    O Susanto
    Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia
    Tissue Antigens 80:477-87. 2012
    ..The significance of the cytotoxic and importantly the non-cytotoxic roles of Grz will be discussed in this review, detailing accepted and controversial functions...
  29. ncbi request reprint Lack of apoptosis of S├ęzary cells in the circulation following oral bexarotene therapy
    S Brennand
    Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, University of Melbourne, Australia
    Br J Dermatol 152:1199-205. 2005
    ..Apoptosis of malignant cells has been suggested as an important mechanism of the action of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL)...
  30. doi request reprint Perforin deficiency and susceptibility to cancer
    A J Brennan
    Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia
    Cell Death Differ 17:607-15. 2010
    ..This review discusses the pathological manifestations of CL deficiencies due to impaired perforin function and describes novel aspects of perforin biology...
  31. pmc Granzymes, cytotoxic granules and cell death: the early work of Dr. Jurg Tschopp
    J A Trapani
    Cancer Cell Death Laboratory, Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
    Cell Death Differ 19:21-7. 2012
    ....
  32. ncbi request reprint A fresh look at tumor immunosurveillance and immunotherapy
    M J Smyth
    Cancer Immunology, Trescowthick Laboratories, Peter MacCallum Cancer Institute, Locked Bag 1, A Beckett St, 8006, Australia
    Nat Immunol 2:293-9. 2001
    ....
  33. doi request reprint Absence of retroviral vector-mediated transformation of gene-modified T cells after long-term engraftment in mice
    J A Westwood
    Cancer Immunology Research Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
    Gene Ther 15:1056-66. 2008
    ..This study indicates that the use of retroviral vectors to transduce T cells does not lead to malignant transformation...
  34. ncbi request reprint Lymphocyte-mediated immunosurveillance of epithelial cancers?
    M J Smyth
    Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Institute, Locked Bag 1, A Beckett St, 8006, Australia
    Trends Immunol 22:409-11. 2001
    ..These findings have rejuvenated interest in the immunosurveillance of tumors, and recent data have provided evidence that the immune system influences the development of some spontaneous epithelial malignancies...
  35. ncbi request reprint Apoptosis induced by the lymphocyte effector molecule perforin
    Paul Bolitho
    Cancer Immunology Program, Peter MacCallum Cancer Centre, St Andrew s Place, East Melbourne, Victoria, Australia
    Curr Opin Immunol 19:339-47. 2007
    ..This clinical picture has prompted further work to uncover the molecular structure of perforin and to define its precise role in immune regulation and immunopathology...
  36. ncbi request reprint Perforin activity and immune homeostasis: the common A91V polymorphism in perforin results in both presynaptic and postsynaptic defects in function
    Ilia Voskoboinik
    Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Australia
    Blood 110:1184-90. 2007
    ..These findings provide the first direct evidence that hPRF-A91V is functionally abnormal and provides a rationale for why it may be responsible for disordered immune homeostasis if inherited with another dysfunctional perforin allele...
  37. pmc Residual active granzyme B in cathepsin C-null lymphocytes is sufficient for perforin-dependent target cell apoptosis
    Vivien R Sutton
    Cancer Immunology Program, Research Division, Peter MacCallum Cancer Centre, East Melbourne, Vic, Australia
    J Cell Biol 176:425-33. 2007
    ..Cathepsin C deficiency also results in considerably milder immune deficiency than perforin or granzyme A/B deficiency...
  38. pmc The major human and mouse granzymes are structurally and functionally divergent
    Dion Kaiserman
    Department of Biochemistry and Molecular Biology and 2Victorian Bioinformatics Consortium, Monash University, Victoria 3800, Australia
    J Cell Biol 175:619-30. 2006
    ..These results demonstrate that even "orthologous" granzymes have species-specific functions, having evolved in distinct environments that pose different challenges...
  39. ncbi request reprint Cytotoxic T-cells from T-cell receptor transgenic NOD8.3 mice destroy beta-cells via the perforin and Fas pathways
    Nadine L Dudek
    St Vincent s Institute, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia
    Diabetes 55:2412-8. 2006
    ..Therefore, NOD8.3 T-cells use both perforin and Fas pathways to kill beta-cells and the surprising blockade of NOD8.3 T-cell-mediated beta-cell death by SOCS-1 overexpression may be due in part to reduced target cell recognition...
  40. ncbi request reprint Cytotoxic T lymphocytes from cathepsin B-deficient mice survive normally in vitro and in vivo after encountering and killing target cells
    Katherine Baran
    Cancer Immunology Program, Peter MacCallum Cancer Centre, St Andrew s Place, East Melbourne 3002, Victoria, Australia
    J Biol Chem 281:30485-91. 2006
    ..We conclude that cathepsin B is not essential for protection of cytotoxic lymphocytes from the toxic effects of their secreted perforin...
  41. ncbi request reprint Granzyme B-mediated death of pancreatic beta-cells requires the proapoptotic BH3-only molecule bid
    Eugene Estella
    St Vincent s Institute, 41 Victoria Parade, Fitzroy, Victoria, 3065, Australia
    Diabetes 55:2212-9. 2006
    ..Our data suggest that Bid cleavage by granzyme B precedes mitochondrial disruption and apoptosis in pancreatic islets...
  42. pmc Cytotoxic T lymphocyte-induced killing in the absence of granzymes A and B is unique and distinct from both apoptosis and perforin-dependent lysis
    Nigel J Waterhouse
    Cancer Cell Death Laboratory, Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria 8006, Australia
    J Cell Biol 173:133-44. 2006
    ..Therefore, CTLs from granzyme AB(-/-) mice induce target cell death by a unique mechanism that is distinct from both perforin lysis and apoptosis...
  43. ncbi request reprint Perforin and Fas induced by IFNgamma and TNFalpha mediate beta cell death by OT-I CTL
    Mark D McKenzie
    St Vincent s Institute, Fitzroy, Melbourne, Australia
    Int Immunol 18:837-46. 2006
    ..However, in the absence of perforin, the Fas/FasL pathway provides an alternative mechanism dependent on islet cell Fas upregulation by cytokines IFNgamma and TNFalpha...
  44. ncbi request reprint The granzyme B gene is highly polymorphic in wild mice but essentially invariant in common inbred laboratory strains
    Kevin Y T Thia
    Cancer Immunology Program, Peter MacCallum Cancer Centre, St Andrew s Place, A Beckett Street, East Melbourne 8006, Australia
    Tissue Antigens 70:198-204. 2007
    ..Unlike the protease, the extended granzyme B recognition and cleavage site in Bid, a key pro-apoptotic substrate, was invariant...
  45. ncbi request reprint Infective, neoplastic, and homeostatic sequelae of the loss of perforin function in humans
    Joseph A Trapani
    Peter MacCallum Cancer Centre, St Andrew s Place, East Melbourne, Australia
    Adv Exp Med Biol 601:235-42. 2007
    ..This chapter discusses the significance of human perforin polymorphisms, particularly those associated with diseases other than FHL, and recent advances in our understanding of perforin biology and function...
  46. ncbi request reprint Sustained antigen-specific antitumor recall response mediated by gene-modified CD4+ T helper-1 and CD8+ T cells
    Maria Moeller
    Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
    Cancer Res 67:11428-37. 2007
    ..These data support the use of gene-modified CD4(+) Th1 and CD8(+) T cells for mediating a sustained antitumor response...
  47. ncbi request reprint Cytotoxic cell granule-mediated apoptosis: perforin delivers granzyme B-serglycin complexes into target cells without plasma membrane pore formation
    Sunil S Metkar
    Evanston Northwestern Healthcare Research Institute, Evanston, IL 60201, USA
    Immunity 16:417-28. 2002
    ....
  48. ncbi request reprint Functional role of phosphatidylinositol 3-kinase in direct tumor lysis by human natural killer cells
    Bin Zhong
    H Lee Moffitt Cancer Center, Department of Interdisciplinary Oncology, University of South Florida College of Medicine, Tampa 33612, USA
    Immunobiology 205:74-94. 2002
    ..These results taken together demonstrate that PI 3-kinase may control NK lytic function via granule polarization towards the contacted target cell...
  49. pmc Suppression of lymphoma and epithelial malignancies effected by interferon gamma
    Shayna E A Street
    Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria 8006, Australia
    J Exp Med 196:129-34. 2002
    ..A significant incidence of late onset adenocarcinoma observed in both IFN-gamma- and pfp-deficient mice indicated that some epithelial tissues were also subject to immunosurveillance...
  50. ncbi request reprint Single-chain antigen recognition receptors that costimulate potent rejection of established experimental tumors
    Nicole M Haynes
    Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, Royal Melbourne Hospital Research Foundation, A Beckett Street, Victoria, Australia 8006
    Blood 100:3155-63. 2002
    ..Our study has illustrated the practical advantage of engineering a T-cell signaling complex that codelivers CD28 activation, dependent only upon the tumor's expression of the appropriate tumor associated antigen...
  51. ncbi request reprint Rejection of syngeneic colon carcinoma by CTLs expressing single-chain antibody receptors codelivering CD28 costimulation
    Nicole M Haynes
    Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, St Andrew s Place, East Melbourne, Victoria, Australia
    J Immunol 169:5780-6. 2002
    ....
  52. doi request reprint Granzyme K expressing cytotoxic T lymphocytes protects against influenza virus in granzyme AB-/- mice
    Misty R Jenkins
    Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia
    Viral Immunol 21:341-6. 2008
    ..This suggests that grzK plays an important role in CD8(+) T-cell cytotoxicity both in the presence and absence of grzA and B...
  53. ncbi request reprint A functional analysis of the putative polymorphisms A91V and N252S and 22 missense perforin mutations associated with familial hemophagocytic lymphohistiocytosis
    Ilia Voskoboinik
    Cancer Immunology Program, Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett St, Melbourne, VIC 8006, Australia
    Blood 105:4700-6. 2005
    ..This report represents the first systematic functional analysis of HLH-associated missense mutations and the 2 most common perforin polymorphisms...
  54. ncbi request reprint Caspase activation by granzyme B is indirect, and caspase autoprocessing requires the release of proapoptotic mitochondrial factors
    Vivien R Sutton
    Cancer Immunology Program, Peter MacCallum Cancer Institute, Locked Bag 1, A Beckett Street, 8006, Melbourne, Australia
    Immunity 18:319-29. 2003
    ....
  55. ncbi request reprint A critical role for granzyme B, in addition to perforin and TNFalpha, in alloreactive CTL-induced mouse pancreatic beta cell death
    Vivien R Sutton
    Cancer Immunology Program, Research Division, Peter MacCallum Cancer Centre, East Melbourne, Australia
    Transplantation 81:146-54. 2006
    ....
  56. ncbi request reprint Role of Bid-induced mitochondrial outer membrane permeabilization in granzyme B-induced apoptosis
    Nigel J Waterhouse
    Cancer Cell Death Laboratory, Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
    Immunol Cell Biol 84:72-8. 2006
    ..In this study, we discuss our recent findings on granzyme B-induced cell death and discuss the potential relevance of this pathway to CL-induced death of viral-infected and transformed cells...
  57. ncbi request reprint Discordant regulation of granzyme H and granzyme B expression in human lymphocytes
    Karin A Sedelies
    Cancer Immunology Laboratory, Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett Street, East Melbourne, 8006, Australia
    J Biol Chem 279:26581-7. 2004
    ..The finding that granzyme H is frequently more abundant than granzyme B in NK cells is consistent with a role for granzyme H in complementing the pro-apoptotic function of granzyme B in human NK cells...
  58. ncbi request reprint Cytotoxic activity of the lymphocyte toxin granzyme B
    Michelle E Wowk
    Cancer Cell Death Laboratory, Cancer Immunology Program, Peter MacCallum Cancer Centre, St Andrew s Place, East Melbourne 3002, Australia
    Microbes Infect 6:752-8. 2004
    ..One of the most potent of these toxins is the serine protease granzyme B. This review will discuss mechanisms used by granzyme B to enter target cells and the ways in which it synergizes with other granule toxins to cause cell death...
  59. ncbi request reprint Gene-engineered T cells as a superior adjuvant therapy for metastatic cancer
    Michael H Kershaw
    Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
    J Immunol 173:2143-50. 2004
    ..T cell adjuvant treatment of day 8 metastatic disease resulted in dramatic increases in survival of mice, and this survival was significantly greater than that afforded by either doxorubicin, 5-fluorouracil, or herceptin...
  60. ncbi request reprint Cytotoxic lymphocytes; instigators of dramatic target cell death
    Nigel J Waterhouse
    Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett St, Melbourne, VIC 8006, Australia
    Biochem Pharmacol 68:1033-40. 2004
    ....
  61. pmc The functional basis for hemophagocytic lymphohistiocytosis in a patient with co-inherited missense mutations in the perforin (PFN1) gene
    Ilia Voskoboinik
    Cancer Immunology Program, Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett St, 8006, Australia
    J Exp Med 200:811-6. 2004
    ..This study elucidates the cellular basis for perforin dysfunctions in hemophagocytic lymphohistiocytosis and provides the means for studying structure-function relationships for lymphocyte perforin...
  62. ncbi request reprint A central role for Bid in granzyme B-induced apoptosis
    Nigel J Waterhouse
    Cancer Cell Death, Gene Regulation, and Immune Signaling Laboratories, Cancer Immunology Program, Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett Street, Melbourne, Victoria 8006
    J Biol Chem 280:4476-82. 2005
    ..Unlike wild type cells, Bid-deficient cells survived and were then able to proliferate normally, demonstrating the critical role for Bid in mediating granzyme B-induced apoptosis...
  63. ncbi request reprint Granzyme B encoded by the commonly occurring human RAH allele retains pro-apoptotic activity
    Jiuru Sun
    Department of Biochemistry and Molecular Biology, Monash University, Melbourne 3800, Victoria, Australia
    J Biol Chem 279:16907-11. 2004
    ..We conclude that the RAH allele represents a neutral polymorphism in the GrB gene...
  64. ncbi request reprint Granzyme M mediates a novel form of perforin-dependent cell death
    Janice M Kelly
    Cancer Immunology Program, Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett St, 8006 Victoria, Australia
    J Biol Chem 279:22236-42. 2004
    ..These data raise the likelihood that granzyme M represents a third major and specialized perforin-dependent cell death pathway that plays a significant role in death mediated by NK cells...
  65. ncbi request reprint Adoptive transfer of gene-engineered CD4+ helper T cells induces potent primary and secondary tumor rejection
    Maria Moeller
    Cancer Immunology Program, Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett St, East Melbourne, 8006, Victoria, Australia
    Blood 106:2995-3003. 2005
    ..Overall, this study has highlighted the therapeutic potential of using combined transfer of antigen-specific gene-modified CD8+ and CD4+ T cells to significantly enhance T-cell adoptive transfer strategies for cancer therapy...
  66. pmc Cationic sites on granzyme B contribute to cytotoxicity by promoting its uptake into target cells
    Catherina H Bird
    Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Australia
    Mol Cell Biol 25:7854-67. 2005
    ..In this electrostatic "exchange-adsorption" model, cs1 and cs2 participate in binding of GrB to the cell surface, thereby promoting its uptake and eventual release into the cytoplasm...
  67. ncbi request reprint Cutting edge: granzymes A and B are not essential for perforin-mediated tumor rejection
    Mark J Smyth
    Cancer Immunology Program, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia
    J Immunol 171:515-8. 2003
    ....
  68. ncbi request reprint The dual adverse effects of TGF-beta secretion on tumor progression
    Joseph A Trapani
    Cancer Immunology Program, Peter MacCallum Cancer Centre, St Andrew s Place, East Melbourne, 3002, Australia
    Cancer Cell 8:349-50. 2005
    ..The findings described below suggest that TGF-beta and its signaling pathways will be major targets for novel cancer therapeutics...
  69. pmc Adoptive transfer of T cells modified with a humanized chimeric receptor gene inhibits growth of Lewis-Y-expressing tumors in mice
    Jennifer A Westwood
    Cancer Immunology Program and Department of Hematology and Medical Oncology, Peter MacCallum Cancer Centre, St Andrew s Place, Melbourne, Victoria 3002, Australia
    Proc Natl Acad Sci U S A 102:19051-6. 2005
    ..This study supports the use of humanized gene-modified T cells as a potential therapy for Le(Y+) malignancies...
  70. ncbi request reprint Purification of natural killer cell cytotoxic granules for assaying target cell apoptosis
    Joanne E Davis
    The Cancer Immunology Research Laboratory, The Peter MacCallum Cancer Institute, Victoria, Melbourne, Australia
    J Immunol Methods 276:59-68. 2003
    ....
  71. ncbi request reprint Report on apoptosis and immunity, 31 May-3 June 2005, Palm Cove, Queensland, Australia
    Joseph A Trapani
    Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
    Immunol Cell Biol 84:1-5. 2006
    ..More than 80 delegates from 20 countries attended the conference, which was held in the convivial surroundings of the Novotel Resort at Palm Cove, north Queensland...
  72. ncbi request reprint Assaying cytochrome C translocation during apoptosis
    Nigel J Waterhouse
    Cancer Immunology, Research Division, Peter MacCallum Cancer Center, Melbourne, Australia
    Methods Mol Biol 284:307-13. 2004
    ..In this chapter, we highlight separation of cytosolic and mitochondrial fractions of cultured cells using digitonin as the method for measuring cytochrome c release that, in our hands has been the simplest and most reproducible...
  73. ncbi request reprint A functional role for CD28 costimulation in tumor recognition by single-chain receptor-modified T cells
    Maria Moeller
    Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, Victoria, Australia
    Cancer Gene Ther 11:371-9. 2004
    ....
  74. pmc The MACPF/CDC family of pore-forming toxins
    Carlos J Rosado
    Department of Biochemistry, Monash University, Clayton, Victoria 3800, Australia
    Cell Microbiol 10:1765-74. 2008
    ..Together with biochemical studies, these structural data suggest that lytic MACPF proteins use a CDC-like mechanism of membrane disruption, and will help understand the roles these proteins play in immunity and development...
  75. doi request reprint The role of p202 in regulating hematopoietic cell proliferation and differentiation
    Louise E Ludlow
    Gene Regulation Laboratory, Peter MacCallum Cancer Centre, East Melbourne VIC 3002, Australia
    J Interferon Cytokine Res 28:5-11. 2008
    ..Thus, p202 plays a role in regulating the proliferative capacity of hematopoietic cells...
  76. ncbi request reprint Addressing the mysteries of perforin function
    Ilia Voskoboinik
    Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
    Immunol Cell Biol 84:66-71. 2006
    ..This article addresses recent key advances in genetic, clinical and biochemical studies that have reignited the current interest in perforin biology...
  77. doi request reprint Measuring cell death mediated by cytotoxic lymphocytes or their granule effector molecules
    Vivien R Sutton
    Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett Street, Melbourne, VIC 8006, Australia
    Methods 44:241-9. 2008
    ..As cell death mediated through TNF-superfamily members and their respective receptors is covered elsewhere, this manuscript will deal specifically with cytotoxic granule-mediated cell death...
  78. ncbi request reprint Novel mechanisms of apoptosis induced by histone deacetylase inhibitors
    Melissa J Peart
    Cancer Immunology Program, The Peter MacCallum Cancer Institute, East Melbourne 3002, Victoria, Australia
    Cancer Res 63:4460-71. 2003
    ....
  79. ncbi request reprint Extracellular matrix remodeling by human granzyme B via cleavage of vitronectin, fibronectin, and laminin
    Marguerite S Buzza
    Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Australia
    J Biol Chem 280:23549-58. 2005
    ..It may also contribute to tissue destruction in diseases in which extracellular GrB is evident, such as rheumatoid arthritis and atherosclerosis...
  80. ncbi request reprint Interaction of the nuclear localizing cytolytic granule serine protease granzyme B with importin alpha or beta: modulation by the serpin inhibitor PI-9
    Elizabeth J Blink
    Nuclear Signalling Laboratory, Division for Biochemistry and Molecular Biology, John Curtin School of Medical Research, Canberra City, Australia
    J Cell Biochem 95:598-610. 2005
    ..We conclude that GrB nuclear import exhibits complex regulation by IMPs; that heterodimerization with PI-9 can modulate the interaction has implications for protection against apoptosis...
  81. ncbi request reprint A common fold mediates vertebrate defense and bacterial attack
    Carlos J Rosado
    Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
    Science 317:1548-51. 2007
    ..Sequence similarity between bacterial and vertebrate MACPF domains suggests that the fold of the CDCs, a family of proteins important for bacterial pathogenesis, is probably used by vertebrates for defense against infection...
  82. ncbi request reprint Perforin-mediated target-cell death and immune homeostasis
    Ilia Voskoboinik
    Cancer Immunology Program, Peter MacCallum Cancer Centre, St Andrew s Place, East Melbourne, Victoria 3002, Australia
    Nat Rev Immunol 6:940-52. 2006
    ..This Review describes recent progress in defining the structure, function, biochemistry and cell biology of perforin...
  83. ncbi request reprint Cloning and characterisation of Ifi206: a new murine HIN-200 family member
    Louise E Ludlow
    Cancer Immunology Program, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria, Australia
    J Cell Biochem 103:1270-82. 2008
    ....
  84. pmc Ligation of the cell surface receptor, CD46, alters T cell polarity and response to antigen presentation
    Jane Oliaro
    Immune Signalling Laboratory, Peter MacCallum Cancer Centre, Faculty of Medicine, University of Melbourne, St Andrew s Place, East Melbourne, VIC 3010, Australia
    Proc Natl Acad Sci U S A 103:18685-90. 2006
    ..These data indicate that external signals can alter lymphocyte polarization toward antigen-presenting cells or target cells, inhibiting lymphocyte function...
  85. ncbi request reprint Calcium-dependent plasma membrane binding and cell lysis by perforin are mediated through its C2 domain: A critical role for aspartate residues 429, 435, 483, and 485 but not 491
    Ilia Voskoboinik
    Cancer Immunology Program, Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett St 8006 and The Walter and Eliza Hall Institute for Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
    J Biol Chem 280:8426-34. 2005
    ..Finally, after experimentally verifying an optimized three-dimensional model, we have made predictions on the impact of two inherited perforin mutations of the C2 domain on calcium-dependent lipid binding and cell lysis...
  86. ncbi request reprint H is for helper: granzyme H helps granzyme B kill adenovirus-infected cells
    Nigel J Waterhouse
    Cancer Cell Death Laboratory, Cancer Immunology Program, Peter MacCallum Cancer Centre, St Andrew s Place, Melbourne, Victoria 3002, Australia
    Trends Immunol 28:373-5. 2007
    ....