2010
DOI: 10.1038/cdd.2009.212
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Perforin deficiency and susceptibility to cancer

Abstract: Cytotoxic lymphocytes (CLs) are the killer cells that destroy intracellular pathogen-infected and transformed cells, predominantly through the cytotoxic granule-mediated death pathway. Soluble cytotoxic granule components, including pore-forming perforin and pro-apoptotic serine proteases, granzymes, synergize to induce unscheduled apoptosis of the target cell. A complete loss of CL function results in an aggressive immunoregulatory disorder, familial hemophagocytic lymphohistiocytosis, whereas a partial loss … Show more

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Cited by 62 publications
(68 citation statements)
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References 93 publications
(127 reference statements)
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“…28 Additionally, perforin deficiency increases the susceptibility to cancer. 13 Indeed, these concepts are consistent with our present findings, in that CD8+ CTL and NK cells from malignant PF have elevated intracellular expression of CD94/NKG2A (i.e. activated form of receptor), undetectable perforin expression and a reduced ability to lyse tumour target cells.…”
Section: Discussionsupporting
confidence: 93%
See 1 more Smart Citation
“…28 Additionally, perforin deficiency increases the susceptibility to cancer. 13 Indeed, these concepts are consistent with our present findings, in that CD8+ CTL and NK cells from malignant PF have elevated intracellular expression of CD94/NKG2A (i.e. activated form of receptor), undetectable perforin expression and a reduced ability to lyse tumour target cells.…”
Section: Discussionsupporting
confidence: 93%
“…Perforin forms pores in the plasma membrane of target cell allowing granzymes types of serine proteases, to enter the target cell, which then activates a series of enzymes, the caspase cascade that eventually lead to apoptosis. 13 Human NK cells are generally recognised as sentinels of the innate immune system due to their inherent capacity to deal with diseased (stressed) cells, including malignant cells. 14 More than 90% of circulating NK cells express moderate levels of CD56 (CD56dim NK cells) and high levels of CD16 and are heterogeneous in the expression of CD94 and NKG2A molecules.…”
Section: Discussionmentioning
confidence: 99%
“…[15,16,17] Perforin mutations resulting in the decrease or absence of the protein or its activity cause the uncontrolled cellular proliferation or lymphoproliferative disorders. [7,18] EBV infection is closely correlated to lymphoma in some cases.…”
Section: Discussionmentioning
confidence: 99%
“…Indeed, as discussed by Brennan et al, 6 a complete loss of cytotoxic lymphocyte perforin function results in familial haemophagocytic lymphohistiocytosis, while a partial loss of perforin function appears to strongly predispose patients to haematological malignancies. However, although perforin knockout mice are susceptible to tumorigenesis, the same cannot be said for single granzyme knockout mice, suggesting that it is necessary to prevent the internalization of multiple granzymes and/or other factors to attenuate tumour clearance.…”
mentioning
confidence: 99%