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Notes
- Abstract:
- Type 1 or invariant NKT (iNKT) cell agonists, epitomized by α-galactosylceramide, protect against cancer largely by IFNγ–dependent mechanisms. Here we describe what we believe to be a novel IFN-γ–independent mechanism induced by -mannosylceramide, which also defines a potentially new class of iNKT cell agonist, with an unusual β-linked sugar. Like -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
- General Note:
- Published IN: Journal of clinical investigation. Volume 121, no. 2 (2011 February).
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