Natural Killer Dendritic Cells Enhance Immune Responses Elicited by α-Galactosylceramide-Stimulated Natural Killer T Cells

Abstract EN

Natural killer dendritic cells (NKDCs) possess potent anti-tumor activity, but the cellular effect of NKDC interactions with other innate immune cells is unclear.

In this study, we demonstrate that the interaction of NKDCs and natural killer T (NKT) cells is required for the anti-tumor immune responses that are elicited by α-galactosylceramide (α-GC) in mice.

The rapid and strong expression of interferon-γ by NKDCs after α-GC stimulation was dependent on NKT cells.

Various NK and DC molecular markers and cytotoxic molecules were up-regulated following α-GC administration.

This up-regulation could improve NKDC presentation of tumor antigens and increase cytotoxicity against tumor cells.

NKDCs were required for the stimulation of DCs, NK cells, and NKT cells.

The strong anti-tumor immune responses elicited by α-GC may be due to the down-regulation of regulatory T cells.

Furthermore, the depletion of NKDCs dampened the tumor clearance mediated by α-GC-stimulated NKT cells in vivo.

Taken together, these results indicate that complex interactions of innate immune cells might be required to achieve optimal anti-tumor immune responses during the early stages of tumorigenesis.