Dendritic cells (DCs) loaded with
alpha-galactosylceramide (
alpha-GalCer) are known to be active APCs for the stimulation of innate NKT and NK cell responses in vivo. In this study, we evaluated the capacity of non-DCs to present
alpha-GalCer in vitro and in vivo, particularly
tumor cells loaded with
alpha-GalCer (
tumor/Gal). Even though the
tumor cells lacked expression of CD40, CD80, and CD86 costimulatory molecules, the i.v. injection of
tumor/Gal resulted in IFN-gamma secretion by NKT and NK cells. These innate responses to
tumor/Gal, including the induction of IL-12p70, were comparable to or better than
alpha-GalCer-loaded DCs.
B16 melanoma cells that were stably transduced to express higher levels of CD1d showed an increased capacity relative to wild-type B16 cells to present
alpha-GalCer in vivo. Three different tumor cell lines, when loaded with
alpha-GalCer, failed to establish
tumors upon i.v. injection, and the mice survived for at least 6 mo. The resistance against
tumor cells was independent of CD4 and CD8 T cells but dependent upon NKT and NK cells. Mice were protected from the development of
metastases if the administration of live B16
tumor cells was followed 3 h or 3 days later by the injection of CD1d(high)-alpha-GalCer-loaded B16
tumor cells with or without irradiation. Taken together, these results indicate that
tumor/Gal are effective APCs for innate NKT and NK cell responses, and that these innate immune responses are able to resist the establishment of
metastases in vivo.