Perforin-mediated cytotoxicity is critical for surveillance of spontaneous lymphoma

Smyth, MJ, Thia, KYT, Street, SEA, MacGregor, D, Godfrey, DI and Trapani, JA (2000) Perforin-mediated cytotoxicity is critical for surveillance of spontaneous lymphoma. Journal of Experimental Medicine, 192 5: 755-760. doi:10.1084/jem.192.5.755

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Author Smyth, MJ
Thia, KYT
Street, SEA
MacGregor, D
Godfrey, DI
Trapani, JA
Title Perforin-mediated cytotoxicity is critical for surveillance of spontaneous lymphoma
Journal name Journal of Experimental Medicine   Check publisher's open access policy
ISSN 0022-1007
Publication date 2000
Sub-type Article (original research)
DOI 10.1084/jem.192.5.755
Open Access Status File (Publisher version)
Volume 192
Issue 5
Start page 755
End page 760
Total pages 6
Language eng
Abstract Immune surveillance by cytotoxic lymphocytes against cancer has been postulated for decades, but direct evidence for the role of cytotoxic lymphocytes in protecting against spontaneous malignancy has been lacking. As the rejection of many experimental cancers by cytotoxic T lymphocytes and natural killer cells is dependent on the pore-forming protein perforin (pfp), we examined pfp-deficient mice for increased cancer susceptibility. Here we show that pfp-deficient mice have a high incidence of malignancy in distinct lymphoid cell lineages (T, B, NKT), indicating a specific requirement for pfp in protection against lymphomagenesis. The susceptibility to lymphoma was accentuated by simultaneous lack of expression of the p53 gene, mutations in which also commonly predispose to human malignancies, including lymphoma. In contrast, the incidence and age of onset of sarcoma was unaffected in p53-deficient mice. Pfp-deficient mice were at least 1,000-fold more susceptible to these lymphomas when transplanted, compared with immunocompetent mice in which tumor rejection was controlled by CD8(+) T lymphocytes. This study is the first that implicates direct cytotoxicity by lymphocytes in regulating lymphomagenesis.
Keyword Immunology
Medicine, Research & Experimental
Tumor Immunity
Perforin
Lymphoma
Cytotoxic T Lymphocyte
Surveillance
Natural-killer-cells
T-cells
Tumor Surveillance
Interferon-gamma
Deficient Mice
P53
Gene
Mutations
Tumorigenesis
Expression
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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Created: Mon, 13 Aug 2007, 11:57:11 EST