Natural Killer (NK) cells are a type of white blood cell that specifically recognize and destroy tumor cells.
For this reason, NK cell transfer therapy is a promising cancer treatment. Expansion and persistence of donor NK cells correlates with tumor clearance, suggesting that therapeutic efficacy can be enhanced by augmenting NK cell survival.
Now, Whitney Rabacal, Eric Sebzda, Ph.D., and colleagues show in a study published in the Proceedings of the National Academy of Sciences that a transcription factor called KLF2 is critical for NK cell expansion and survival.
They discovered that KLF2 both limits immature NK cell proliferation and instructs mature NK cells to home to niches rich in interleukin 15 (IL-15), which is necessary for their continued survival.
Importantly, this report suggests that tumors avoid immune clearance by promoting KLF2 destruction within the NK cell population, thereby starving these cells of IL-15.
Therefore, recruiting IL-15 transpresenting cells to tumor microenvironments may improve NK cell-mediated cancer therapy by preventing NK cell exhaustion and restoring antitumor immunity.
This research was supported in part by the National Institutes of Health (grant HL069765).