α-GalCer–pulsed DCs activate NKT cells and antiviral T cells in advanced cancer patients.

Mature DCs and the NKT cell ligand α-galactosyl ceramide (α-GalCer) are a promising combination for boosting immunity in humans, according to a study on page 1503. Chang and colleagues used α-GalCer–pulsed DCs to immunize cancer patients and showed that the treatment resulted in long-term expansion of both NKT cells and virus-specific CD8+ T cells.α-GalCer, a glycolipid derived from marine sponges, was identified based on its antitumor properties. This foreign glycolipid was later found to be presented to NKT cells by DCs. NKT cells activated by this glycolipid can promote tumor regression in mice. Attempts to extend this work to humans, however, have met with limited success. α-GalCer treatment alone decreased NKT cell numbers in patients with solid tumors, and vaccination with α-GalCer–pulsed immature DCs induced only modest and transient NKT cell expansion.

Maturation of the DCs—treatment with cytokines that enhance the expression of MHC and costimulatory molecules—was the key to the approach used by Chang and colleagues. They immunized five advanced cancer patients, none of whom had detectable NKT cells in their blood before treatment. But with α-GalCer–pulsed mature DCs, all patients had a rapid and sustained increase in NKT cell numbers.

Surprisingly, CD8+ T cells specific for cytomegalovirus were also expanded by the treatment, suggesting that this approach might also be useful to boost immunity to chronic viral infections like HIV or hepatitis C virus, or to enhance the efficacy of T cell–based vaccines.