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Publication : Different requirements for alpha-galactosylceramide and recombinant IL-12 antitumor activity in the treatment of C-26 colon carcinoma hepatic metastases.

First Author  Chiodoni C Year  2001
Journal  Eur J Immunol Volume  31
Issue  10 Pages  3101-10
PubMed ID  11592087 Mgi Jnum  J:115631
Mgi Id  MGI:3692011 Doi  10.1002/1521-4141(2001010)31:10<3101::aid-immu3101>3.0.co;2-8
Citation  Chiodoni C, et al. (2001) Different requirements for alpha-galactosylceramide and recombinant IL-12 antitumor activity in the treatment of C-26 colon carcinoma hepatic metastases. Eur J Immunol 31(10):3101-10
abstractText  The glycolipid alpha-galactosylceramide (alpha-GalCer), ligand of NKT cells, has been recently shown to induce antitumor immunity in mice through the induction of IL-12 production by dendritic cells. In the present study we compared alpha-GalCer and rIL-12 antitumor activities in the treatment of hepatic metastases of the C-26 murine colon carcinoma. We show that in immunocompetent mice the two molecules display similar efficacy, whereas in mice knockout (KO) for beta2-microglobulin (beta2m), IFN-gamma or IL-12p40, alpha-GalCer antitumor activity is severely impaired. Conversely,in all such KO mice, rIL-12 retains its efficacy. In this context, the IL-12 effect relies on NK cell function since it is abrogated by antibodies to NK1.1, expressed by both NK and NKT cells, but not in beta2m KO mice that lack NKT and CD8 T cells, but have a perfectly functional NK cell population. Furthermore, in IFN-gamma and IL-12p40 double KO mice, exogenous rIL-12 completely loses antitumor efficacy, suggesting the existence of an IFN-gamma-independent IL-12 effect that does require the presence of endogenous IL-12p40 chain.
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