last paper I could find where he was either first or senior author.....
Nature. 2007 Dec 6;450(7171):903-7. Epub 2007 Nov 18.
Adaptive immunity maintains occult cancer in an equilibrium state.
Koebel CM, Vermi W, Swann JB, Zerafa N, Rodig SJ, Old LJ, Smyth MJ, Schreiber RD.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Comment in:
Nature. 2007 Dec 6;450(7171):803-4.
The capacity of immunity to control and shape cancer, that is, cancer immunoediting, is the result of three processes that function either independently or in sequence: elimination (cancer immunosurveillance, in which immunity functions as an extrinsic tumour suppressor in naive hosts); equilibrium (expansion of transformed cells is held in check by immunity); and escape (tumour cell variants with dampened immunogenicity or the capacity to attenuate immune responses grow into clinically apparent cancers). Extensive experimental support now exists for the elimination and escape processes because immunodeficient mice develop more carcinogen-induced and spontaneous cancers than wild-type mice, and tumour cells from immunodeficient mice are more immunogenic than those from immunocompetent mice. In contrast, the equilibrium process was inferred largely from clinical observations, including reports of transplantation of undetected (occult) cancer from organ donor into immunosuppressed recipients. Herein we use a mouse model of primary chemical carcinogenesis and demonstrate that equilibrium occurs, is mechanistically distinguishable from elimination and escape, and that neoplastic cells in equilibrium are transformed but proliferate poorly in vivo. We also show that tumour cells in equilibrium are unedited but become edited when they spontaneously escape immune control and grow into clinically apparent tumours. These results reveal that, in addition to destroying tumour cells and sculpting tumour immunogenicity, the immune system of a naive mouse can also restrain cancer growth for extended time periods.
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So Lloyd Old was an author on that, and this sounds like they're doing the sort of work that I've always wanted to see done. Not that I believe that chemically-induced rodent models are relevant, but.... it's the starting point for most dogma, and somebody needed to go back and pick it apart in context to old work. With respect to.... tumour cells from immunodeficient mice are more immunogenic than those from immunocompetent mice?? Good idea, so simple but had not occurred to me, haven't yet tried to find the published data, would like to do the work with my own hands, ya know?
Thank you!
Rick |
