Mouse and human iNKT cell agonist β-mannosylceramide reveals a distinct mechanism of tumor immunity.
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| Abstract |
Type 1 or invariant NKT (iNKT) cell agonists, epitomized by α-galactosylceramide, protect against cancer largely by IFN-γ-dependent mechanisms. Here we describe what we believe to be a novel IFN-γ-independent mechanism induced by β-mannosylceramide, which also defines a potentially new class of iNKT cell agonist, with an unusual β-linked sugar. Like α-galactosylceramide, β-mannosylceramide directly activates iNKT cells from both mice and humans. In contrast to α-galactosylceramide, protection by β-mannosylceramide was completely dependent on NOS and TNF-α, neither of which was required to achieve protection with α-galactosylceramide. Moreover, at doses too low for either alone to protect, β-mannosylceramide synergized with α-galactosylceramide to protect mice against tumors. These results suggest that treatment with β-mannosylceramide provides a distinct mechanism of tumor protection that may allow efficacy where other agonists have failed. Furthermore, the ability of β-mannosylceramide to synergize with α-galactosylceramide suggests treatment with this class of iNKT agonist may provide protection against tumors in humans.
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| Authors | Jessica J O'Konek, Petr Illarionov, Deborah Stewart Khursigara, Elena Ambrosino, Liat Izhak, Bernard F Castillo 2nd, Ravinder Raju, Maryam Khalili, Hee-Yong Kim, Amy R Howell, Gurdyal S Besra, Steven A Porcelli, Jay A Berzofsky, Masaki Terabe |
| Journal | The Journal of clinical investigation (J Clin Invest) Vol. 121 Issue 2 Pg. 683-94 (Feb 2011) ISSN: 1558-8238 [Electronic] United States |
| PMID | 21245578 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't) |
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