Perforin deficiency and susceptibility to cancer

Cell Death and Differentiation

Volumn 17, Issue 4, 2010, Pages 607-615

  Brennan, A J ^a,b   Chia, J ^a   Trapani, J A ^a,b   Voskoboinik, I ^a,b  

^a PETER MACCALLUM CANCER CENTRE   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Cytotoxic lymphocytes; FHL; Granzyme; Leukemia; Lymphoma

Indexed keywords

GRANZYME A; GRANZYME B; PERFORIN; SYNTAXIN; SYNTAXIN 11; UNCLASSIFIED DRUG;

APOPTOSIS; B CELL LYMPHOMA; CANCER SUSCEPTIBILITY; CARCINOGENESIS; CYTOTOXIC T LYMPHOCYTE; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENETIC VARIABILITY; HEMATOLOGIC MALIGNANCY; HUMAN; IMMUNE RESPONSE; IMMUNOPATHOGENESIS; IMMUNOREGULATION; KILLER CELL; LYMPHOCYTOSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEFICIENCY; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; T CELL LYMPHOMA;

ANIMALS; APOPTOSIS REGULATORY PROTEINS; GENETIC PREDISPOSITION TO DISEASE; GRANZYMES; HUMANS; IMMUNE SYSTEM; IMMUNOLOGIC SURVEILLANCE; LYMPHOHISTIOCYTOSIS, HEMOPHAGOCYTIC; MICE; NEOPLASMS; PORE FORMING CYTOTOXIC PROTEINS; T-LYMPHOCYTES, CYTOTOXIC;

EID: 77949512579     PISSN: 13509047     EISSN: 14765403     Source Type: Journal    
DOI: 10.1038/cdd.2009.212     Document Type: Review

References (94)

1. Kagi D, Vignaux F, Ledermann B, Burki K, Depraetere V, Nagata S et al. Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. Science 1994; 265: 528-530.
2. Trapani JA, Smyth MJ. Functional significance of the perforin/granzyme cell death pathway. Nat Rev Immunol 2002; 2: 735-747.
3. Voskoboinik I, Smyth MJ, Trapani JA. Perforin-mediated target-cell death and immune homeostasis. Nat Rev Immunol 2006; 6: 940-952.
4. Uellner R, Zvelebil MJ, Hopkins J, Jones J, MacDougall LK, Morgan BP et al. Perforin is activated by a proteolytic cleavage during biosynthesis which reveals a phospholipid-binding C2 domain. EMBO J 1997; 16: 7287-7296.
5. Voskoboinik I, Thia MC, Fletcher J, Ciccone A, Browne K, Smyth MJ et al. 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. J Biol Chem 2005; 280: 8426-8434.
6. Mullbacher A, Waring P, ThaHla R, Tran T, Chin S, Stehle T et al. Granzymes are the essential downstream effector molecules for the control of primary virus infections by cytolytic leukocytes. Proc Natl Acad Sci USA 1999; 96: 13950-13955.
7. Nakajima H, Park HL, Henkart PA. Synergistic roles of granzymes A and B in mediating target cell death by rat basophilic leukemia mast cell tumors also expressing cytolysin/ perforin. J Exp Med 1995; 181: 1037-1046.
8. Shi L, Mai S, Israels S, Browne K, Trapani JA, Greenberg AH. Granzyme B (GraB) autonomously crosses the cell membrane and perforin initiates apoptosis and GraB nuclear localization. J Exp Med 1997; 185: 855-866.
9. Stepp SE, Dufourcq-Lagelouse R, Le Deist F, Bhawan S, Certain S, Mathew PA et al. Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science 1999; 286: 1957-1959.
10. Chia J, Yeo KP, Whisstock JC, Dunstone MA, Trapani JA, Voskoboinik I. Temperature sensitivity of human perforin mutants unmasks subtotal loss of cytotoxicity, delayed FHL, and a predisposition to cancer. Proc Natl Acad Sci USA 2009; 106: 9809-9814.
11. Pipkin ME, Ljutic B, Cruz-Guilloty F, Nouzova M, Rao A, Zuniga-Pflucker JC et al. Chromosome transfer activates and delineates a locus control region for perforin. Immunity 2007; 26: 29-41.
12. Hernandez-Pigeon H, Jean C, Charruyer A, Haure MJ, Baudouin C, Charveron M et al. UVA induces granzyme B in human keratinocytes through MIF: implication in extracellular matrix remodeling. J Biol Chem 2007; 282: 8157-8164.
13. Hernandez-Pigeon H, Jean C, Charruyer A, Haure MJ, Titeux M, Tonasso L et al. Human keratinocytes acquire cellular cytotoxicity under UV-B irradiation. Implication of granzyme B and perforin. J Biol Chem 2006; 281: 13525-13532.
14. Podack ER, Dennert G. Assembly of two types of tubules with putative cytolytic function by cloned natural killer cells. Nature 1983; 302: 442-445.
15. Podack ER, Young JD, Cohn ZA. Isolation and biochemical and functional characterization of perforin 1 from cytolytic T-cell granules. Proc Natl Acad Sci USA 1985; 82: 8629-8633.
16. Young JD, Cohn ZA, Podack ER. The ninth component of complement and the pore-forming protein (perforin 1) from cytotoxic T cells: structural, immunological, and functional similarities. Science 1986; 233: 184-190.
17. Young JD, Hengartner H, Podack ER, Cohn ZA. Purification and characterization of a cytolytic pore-forming protein from granules of cloned lymphocytes with natural killer activity. Cell 1986; 44: 849-859.
18. Lowrey DM, Aebischer T, Olsen K, Lichtenheld M, Rupp F, Hengartner H et al. Cloning, analysis, and expression of murine perforin 1 cDNA, a component of cytolytic T-cell granules with homology to complement component C9. Proc Natl Acad Sci USA 1989; 86: 247-251.
19. Shinkai Y, Takio K, Okumura K. Homology of perforin to the ninth component of complement (C9). Nature 1988; 334: 525-527.
20. Tschopp J, Masson D, Stanley KK. Structural/functional similarity between proteins involved in complement-and cytotoxic T-lymphocyte-mediated cytolysis. Nature 1986; 322: 831-834.
21. Lichtenheld MG, Olsen KJ, Lu P, Lowrey DM, Hameed A, Hengartner H et al. Structure and function of human perforin. Nature 1988; 335: 448-451.
22. Blumenthal R, Millard PJ, Henkart MP, Reynolds CW, Henkart PA. Liposomes as targets for granule cytolysin from cytotoxic large granular lymphocyte tumors. Proc Natl Acad Sci USA 1984; 81: 5551-5555.
23. Henkart PA, Yue CC, Yang J, Rosenberg SA. Cytolytic and biochemical properties of cytoplasmic granules of murine lymphokine-activated killer cells. J Immunol 1986; 137: 2611-2617.
24. Pham CT, Ley TJ. Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo. Proc Natl Acad Sci USA 1999; 96: 8627-8632.
25. Smyth MJ, McGuire MJ, Thia KY. Expression of recombinant human granzyme B. A processing and activation role for dipeptidyl peptidase I. J Immunol 1995; 154: 6299-6305.
26. Bird CH, Sutton VR, Sun J, Hirst CE, Novak A, Kumar S et al. Selective regulation of apoptosis: the cytotoxic lymphocyte serpin proteinase inhibitor 9 protects against granzyme B-mediated apoptosis without perturbing the Fas cell death pathway. Mol Cell Biol 1998; 18: 6387-6398.
27. Sun J, Ooms L, Bird CH, Sutton VR, Trapani JA, Bird PI. A new family of 10 murine ovalbumin serpins includes two homologs of proteinase inhibitor 8 and two homologs of the granzyme B inhibitor (proteinase inhibitor 9). J Biol Chem 1997; 272: 15434-15441.
28. Sun J, Bird CH, Sutton V, McDonald L, Coughlin PB, De Jong TA et al. A cytosolic granzyme B inhibitor related to the viral apoptotic regulator cytokine response modifier A is present in cytotoxic lymphocytes. J Biol Chem 1996; 271: 27802-27809.
29. Hirst CE, Buzza MS, Bird CH, Warren HS, Cameron PU, Zhang M et al. The intracellular granzyme B inhibitor, proteinase inhibitor 9, is up-regulated during accessory cell maturation and effector cell degranulation, and its overexpression enhances CTL potency. J Immunol 2003; 170: 805-815.
30. Rosado CJ, Kondos S, Bull TE, Kuiper MJ, Law RH, Buckle AM et al. The MACPF/CDC family of pore-forming toxins. Cell Microbiol 2008; 10: 1765-1774.
31. Hadders MA, Beringer DX, Gros P. Structure of C8alpha-MACPF reveals mechanism of membrane attack in complement immune defense. Science 2007; 317: 1552-1554.
32. Rosado CJ, Buckle AM, Law RH, Butcher RE, Kan WT, Bird CH et al. A common fold mediates vertebrate defense and bacterial attack. Science 2007; 317: 1548-1551.
33. Slade DJ, Lovelace LL, Chruszcz M, Minor W, Lebioda L, Sodetz JM. Crystal structure of the MACPF domain of human complement protein C8 alpha in complex with the C8 gamma subunit. J Mol Biol 2008; 379: 331-342.
34. Baran K, Dunstone M, Chia J, Ciccone A, Browne KA, Clarke CJP et al. The molecular basis for perforin oligomerization and transmembrane pore assembly. Immunity 2009; 30: 684-695.
35. Kagi D, Ledermann B, Burki K, Seiler P, Odermatt B, Olsen KJ et al. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature 1994; 369: 31-37.
36. Smyth MJ, Thia KY, Street SE, MacGregor D, Godfrey DI, Trapani JA. Perforin-mediated cytotoxicity is critical for surveillance of spontaneous lymphoma. J Exp Med 2000; 192: 755-760.
37. Badovinac VP, Hamilton SE, Harty JT. Viral infection results in massive CD8+ T cell expansion and mortality in vaccinated perforin-deficient mice. Immunity 2003; 18: 463-474.
38. Binder D, van den Broek MF, Kagi D, Bluethmann H, Fehr J, Hengartner H et al. Aplastic anemia rescued by exhaustion of cytokine-secreting CD8+ T cells in persistent infection with lymphocytic choriomeningitis virus. J Exp Med 1998; 187: 1903-1920.
39. Kagi D, Seiler P, Pavlovic J, Ledermann B, Burki K, Zinkernagel RM et al. The roles of perforin-and Fas-dependent cytotoxicity in protection against cytopathic and noncytopathic viruses. Eur J Immunol 1995; 25: 3256-3262.
40. Walsh CM, Matloubian M, Liu CC, Ueda R, Kurahara CG, Christensen JL et al. Immune function in mice lacking the perforin gene. Proc Natl Acad Sci USA 1994; 91: 10854-10858.
41. Jordan MB, Hildeman D, Kappler J, Marrack P. An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder. Blood 2004; 104: 735-743.
42. Ebnet K, Hausmann M, Lehmann-Grube F, Mullbacher A, Kopf M, Lamers M et al. Granzyme A-deficient mice retain potent cell-mediated cytotoxicity. EMBO J 1995; 14: 4230-4239.
43. Mullbacher A, Ebnet K, Blanden RV, Hla RT, Stehle T, Museteanu C et al. Granzyme A is critical for recovery of mice from infection with the natural cytopathic viral pathogen, ectromelia. Proc Natl Acad Sci USA 1996; 93: 5783-5787.
44. Simon MM, Hausmann M, Tran T, Ebnet K, Tschopp J, ThaHla R et al. In vitro-and ex vivo-derived cytolytic leukocytes from granzyme A x B double knockout mice are defective in granule-mediated apoptosis but not lysis of target cells. J Exp Med 1997; 186: 1781-1786.
45. Andrade F, Fellows E, Jenne DE, Rosen A, Young CS. Granzyme H destroys the function of critical adenoviral proteins required for viral DNA replication and granzyme B inhibition. EMBO J 2007; 26: 2148-2157.
46. Romero V, Fellows E, Jenne DE, Andrade F. Cleavage of La protein by granzyme H induces cytoplasmic translocation and interferes with La-mediated HCV-IRES translational activity. Cell Death Differ 2009; 16: 340-348.
47. Thia KY, Trapani JA. The granzyme B gene is highly polymorphic in wild mice but essentially invariant in common inbred laboratory strains. Tissue Antigens 2007; 70: 198-204.
48. van den Broek ME, Kagi D, Ossendorp F, Toes R, Vamvakas S, Lutz WK et al. Decreased tumor surveillance in perforin-deficient mice. J Exp Med 1996; 184: 1781-1790.
49. Smyth MJ, Thia KY, Cretney E, Kelly JM, Snook MB, Forbes CA et al. Perforin is a major contributor to NK cell control of tumor metastasis. J Immunol 1999; 162: 6658-6662.
50. Davis JE, Smyth MJ, Trapani JA. Granzyme A and B-deficient killer lymphocytes are defective in eliciting DNA fragmentation but retain potent in vivo anti-tumor capacity. Eur J Immunol 2001; 31: 39-47.
51. Street SE, Cretney E, Smyth MJ. Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 2001; 97: 192-197.
52. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002; 3: 991-998.
53. Street SE, Trapani JA, MacGregor D, Smyth MJ. Suppression of lymphoma and epithelial malignancies effected by interferon gamma. J Exp Med 2002; 196: 129-134.
54. Smyth MJ, Street SE, Trapani JA. Cutting edge: granzymes A and B are not essential for perforin-mediated tumor rejection. J Immunol 2003; 171: 515-518.
55. Street SE, Hayakawa Y, Zhan Y, Lew AM, MacGregor D, Jamieson AM et al. Innate immune surveillance of spontaneous B cell lymphomas by natural killer cells and gammadelta T cells. J Exp Med 2004; 199: 879-884.
56. Koebel CM, Vermi W, Swann JB, Zerafa N, Rodig SJ, Old LJ et al. Adaptive immunity maintains occult cancer in an equilibrium state. Nature 2007; 450: 903-908.
57. Crowe NY, Smyth MJ, Godfrey DI. A critical role for natural killer T cells in immuno-surveillance of methylcholanthrene-induced sarcomas. J Exp Med 2002; 196: 119-127.
58. Molleran Lee S, Villanueva J, Sumegi J, Zhang K, Kogawa K, Davis J et al. Characterisation of diverse PRF1 mutations leading to decreased natural killer cell activity in North American families with haemophagocytic lymphohistiocytosis. J Med Genet 2004; 41: 137-144.
59. Henter JI, Elinder G. Familial hemophagocytic lymphohistiocytosis. Clinical review based on the findings in seven children. Acta Paediatr Scand 1991; 80: 269-277.
60. Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Eur J Pediatr 2007; 166: 95-109.
61. Filipovich AH. Hemophagocytic lymphohistiocytosis and other hemophagocytic disorders. Immunol Allergy Clin North Am 2008; 28: 293-313.
62. Feldmann J, Callebaut I, Raposo G, Certain S, Bacq D, Dumont C et al. Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3). Cell 2003; 115: 461-473.
63. Menager MM, Menasche G, Romao M, Knapnougel P, Ho CH, Garfa M et al. Secretory cytotoxic granule maturation and exocytosis require the effector protein hMunc13-4. Nat Immunol 2007; 8: 257-267.
64. Cote M, Menager MM, Burgess A, Mahlaoui N, Picard C, Schaffner C et al. Munc18-2 deficiency causes familial hemophagocytic lymphohistiocytosis type 5 and impairs cytotoxic granule exocytosis in patient NK cells. J Clin Invest 2009; 119: 3765-3773.
65. zur Stadt U, Rohr J, Seifert W, Koch F, Grieve S, Pagel J et al. Familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) is caused by mutations in Munc18-2 and impaired binding to syntaxin 11. Am J Hum Genet 2009; 85: 482-492.
66. Bryceson YT, Rudd E, Zheng C, Edner J, Ma D, Wood SM et al. Defective cytotoxic lymphocyte degranulation in syntaxin-11 deficient familial hemophagocytic lymphohistiocytosis 4 (FHL4) patients. Blood 2007; 110: 1906-1915.
67. Ishii E, Ohga S, Imashuku S, Kimura N, Ueda I, Morimoto A et al. Review of hemophagocytic lymphohistiocytosis (HLH) in children with focus on Japanese experiences. Crit Rev Oncol Hematol 2005; 53: 209-223.
68. Zur Stadt U, Beutel K, Kolberg S, Schneppenheim R, Kabisch H, Janka G et al. Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A. Hum Mutat 2006; 27: 62-68.
69. Trizzino A, zur Stadt U, Ueda I, Risma K, Janka G, Ishii E et al. Genotype-phenotype study of familial haemophagocytic lymphohistiocytosis due to perforin mutations. J Med Genet 2008; 45: 15-21.
70. Lee SM, Sumegi J, Villanueva J, Tabata Y, Zhang K, Chakraborty R et al. Patients of African ancestry with hemophagocytic lymphohistiocytosis share a common haplotype of PRF1 with a 50delT mutation. J Pediatr 2006; 149: 134-137.
71. Ueda I, Morimoto A, Inaba T, Yagi T, Hibi S, Sugimoto T et al. Characteristic perforin gene mutations of haemophagocytic lymphohistiocytosis patients in Japan. Br J Haematol 2003; 121: 503-510.
72. Mehta PA, Davies SM, Kumar A, Devidas M, Lee S, Zamzow T et al. Perforin polymorphism A91V and susceptibility to B-precursor childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group. Leukemia 2006; 20: 1539-1541.
73. Santoro A, Cannella S, Trizzino A, Lo Nigro L, Corsello G, Arico M. A single amino acid change A91V in perforin: a novel, frequent predisposing factor to childhood acute lymphoblastic leukemia? Haematologica 2005; 90: 697-698.
74. Zur Stadt U, Beutel K, Weber B, Kabisch H, Schneppenheim R, Janka G et al. A91V is a polymorphism in the perforin gene not causative of an FHLH phenotype. Blood 2004; 104: 1909-1910.
75. Muralitharan S, Wali Y, Pathare AV. Perforin A91V polymorphism and putative susceptibility to hematological malignancies. Leukemia 2006; 20: 2178.
76. Clementi R, Locatelli F, Dupre L, Garaventa A, Emmi L, Bregni M et al. A proportion of patients with lymphoma may harbor mutations of the perforin gene. Blood 2005; 105: 4424-4428.
77. Cannella S, Santoro A, Bruno G, Pillon M, Mussolin L, Mangili G et al. Germline mutations of the perforin gene are a frequent occurrence in childhood anaplastic large cell lymphoma. Cancer 2007; 109: 2566-2571.
78. Clementi R, Chiocchetti A, Cappellano G, Cerutti E, Ferretti M, Orilieri E et al. Variations of the perforin gene in patients with autoimmunity/ lymphoproliferation and defective fas function. Blood 2006; 108: 3079-3084.
79. Voskoboinik I, Thia MC, Trapani JA. A functional analysis of the putative polymorphisms A91V and N252S and 22 missense perforin mutations associated with familial hemophagocytic lymphohistiocytosis. Blood 2005; 105: 4700-4706.
80. Voskoboinik I, Sutton VR, Ciccone A, House CM, Chia J, Darcy PK et al. Perforin activity and immune homeostasis: the common A91V polymorphism in perforin results in both presynaptic and postsynaptic defects in function. Blood 2007; 110: 1184-1190.
81. Trambas C, Gallo F, Pende D, Marcenaro S, Moretta L, De Fusco C et al. A single amino acid change, A91V, leads to conformational changes that can impair processing to the active form of perforin. Blood 2005; 106: 932-937.
82. Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007; 48: 124-131.
83. Mancebo E, Allende LM, Guzman M, Paz-Artal E, Gil J, Urrea-Moreno R et al. Familial hemophagocytic lymphohistiocytosis in an adult patient homozygous for A91V in the perforin gene, with tuberculosis infection. Haematologica 2006; 91: 1257-1260.
84. Nagafuji K, Nonami A, Kumano T, Kikushige Y, Yoshimoto G, Takenaka K et al. Perforin gene mutations in adult-onset hemophagocytic lymphohistiocytosis. Haematologica 2007; 92: 978-981.
85. Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet 2000; 356: 1795-1799.
86. Denning MG, Anderson MP, Amara JF, Marshall J, Smith AE, Welsh MJ. Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive. Nature 1992; 358: 761-764.
87. Kagi D, Odermatt B, Ohashi PS, Zinkernagel RM, Hengartner H. Development of insulitis without diabetes in transgenic mice lacking perforin-dependent cytotoxicity. J Exp Med 1996; 183: 2143-2152.
88. Kagi D, Odermatt B, Seiler P, Zinkernagel RM, Mak TW, Hengartner H. Reduced incidence and delayed onset of diabetes in perforin-deficient nonobese diabetic mice. J Exp Med 1997; 186: 989-997.
89. Su X, Hu Q, Kristan JM, Costa C, Shen Y, Gero D et al. Significant role for Fas in the pathogenesis of autoimmune diabetes. J Immunol 2000; 164: 2523-2532.
90. Potter S, Chan-Ling T, Ball HJ, Mansour H, Mitchell A, Maluish L et al. Perforin mediated apoptosis of cerebral microvascular endothelial cells during experimental cerebral malaria. Int J Parasitol 2006; 36: 485-496.
91. Nitcheu J, Bonduelle O, Combadiere C, Tefit M, Seilhean D, Mazier D et al. Perforin-dependent brain-infiltrating cytotoxic CD8+ T lymphocytes mediate experimental cerebral malaria pathogenesis. J Immunol 2003; 170: 2221-2228.
92. Cappellano G, Orilieri E, Comi C, Chiocchetti A, Bocca S, Boggio E et al. Variations of the perforin gene in patients with multiple sclerosis. Genes Immun 2008; 9: 438-444.
93. Deb C, Lafrance-Corey RG, Zoecklein L, Papke L, Rodriguez M, Howe CL. Demyelinated axons and motor function are protected by genetic deletion of perforin in a mouse model of multiple sclerosis. J Neuropathol Exp Neurol 2009; 68: 1037-1048.
94. Trapani JA, Voskoboinik I. The complex issue of regulating perforin expression. Trends Immunol 2007; 28: 243-245.