Host perforin reduces tumor number but does not increase survival in oncogene-driven mammary adenocarcinoma.
The concept of tumor immune surveillance has been supported by several recent studies in mice which show that immune effector mechanisms suppress hematologic malignancy. However, because the most common forms of human cancer are epithelial in origin, and comparatively very little data supports the immune surveillance of epithelial malignancies, we have chosen to evaluate the role of perforin-mediated cytotoxicity in the prevention of BALB/c Her2/neu-induced mammary cancer. Interestingly, perforin significantly delayed the onset of mammary tumorigenesis and reduced the number of mammary tumors without improving survival. Natural killer cell, but not CD8+ T cell, depletion resulted in a similar phenotype to perforin deficiency in this regard. Histologic analysis further indicated that the effect of perforin was most evident during the earliest stages of carcinogenesis rather than prior to or during the hyperplastic phase. This data suggests that perforin may mediate some suppression of epithelial carcinogenesis by intervening early in the tumor development process.
Street
Shayna E A
SE
Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
Zerafa
Nadeen
N
Iezzi
Manuela
M
Westwood
Jennifer A
JA
Stagg
John
J
Musiani
Piero
P
Smyth
Mark J
MJ
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology; D005260:Female; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009857:Oncogenes; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000276:immunology
D008562:Membrane Glycoproteins; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases