A report on page 1279 suggests that, for antitumor immunity, all natural killer T (NKT) cells are not created equal. Crowe and colleagues show that a subset of liver-derived NKT cells is uniquely equipped to fight off tumors.

NKT cells are innate immune cells known for their rapid production of both T helper (Th) 1 and Th2 cytokines upon stimulation. NKT cells can either promote or suppress immune responses, likely depending upon which cytokines the cells predominantly produce. Subsets of NKT cells have been identified (based on the expression of CD4) that have distinct cytokine production profiles in vitro. But whether these subsets are functionally distinct in vivo had not been tested.

In their previous work, this group had shown that NKT cells from the liver were able to combat tumors in mice. They now show that it is only CD4 NKT cells from the liver than can promote tumor rejection. CD4+ NKT cells from the liver and both CD4+ and CD4 NKT cells derived from the spleen or thymus were ill equipped for the job.

The authors are now trying to determine what sets the CD4 liver NKT cells apart from the rest, as cytokine production among the NKT cell subsets was comparable. In the meantime, the identification of a specialized antitumor subset of NKT cells may provide a way to improve upon current NKT cell–based tumor therapies.