OX40 signaling directly triggers the antitumor effects of NKT cells.

Pathways involving the costimulatory molecule OX40 and OX40 ligand (OX40L) enhance tumor rejection. It was presumed that this effect was mediated by changes in DCs and/or T cells. In this issue of the JCI, Zaini et al. report that, in mice, intratumoral injection of DCs genetically modified to express OX40L suppressed the growth of a preexisting melanoma by directly triggering an antitumor NKT cell response (see the related article beginning on page 3330). This work suggests that the intratumoral NKT cell population may be harnessed for cancer immunotherapy and that OX40 costimulation may be used as a unique trigger of the antitumor activity of these cells.