Perforin deficiency and susceptibility to cancer.
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 of function seems to be a factor strongly predisposing to hematological malignancies. This review discusses the pathological manifestations of CL deficiencies due to impaired perforin function and describes novel aspects of perforin biology.
Brennan
A J
AJ
Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia.
Chia
J
J
Trapani
J A
JA
Voskoboinik
I
I
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000201:enzymology / Q000503:physiopathology; D007157:Immunologic Surveillance / Q000502:physiology*; D051359:Lymphohistiocytosis, Hemophagocytic / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000172:deficiency* / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology* / Q000276:immunology
D051017:Apoptosis Regulatory Proteins; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D053804:Granzymes