Natural killer (NK) cell-mediated therapy remains a promising way to treat cancers of the blood. Now scientists at Vanderbilt University Medical Center report an important factor--Kruppel-like factor 2 (KLF2)--whose absence holds back NK cells from carrying out their job of clearing invading cancer cells.
Eric Sebzda and his research team at Vanderbilt University published their work in the Proceedings of the National Academy of Sciences.
NK cells, a type of white blood cell involved in our innate defense against pathogens, are able to seek out and destroy cancer cells in our blood. Using NK cell-mediated tumor therapy is an attractive approach in the clinic, but so far remission rates after therapy remain high.
They identified a protein called KLF2, a transcription factor that they say regulates NK cell expansion and survival. In a mouse model they found that genetically deleting the Klf2 gene worsens NK cells' ability to proliferate and survive.
"This is the same process likely used by cancer cells to avoid destruction by NK cells," Sebzda said in a university news release, referring to the Klf2 genetic mouse model.
KLF2 was found to limit immature NK cell proliferation and chaperone mature NK cells to microenvironments high in interleukin 15 (IL-15). One approach would be to increase the amount of IL-15, which would improve the immune response against tumors. The researchers emphasize the need to target IL-15 specifically to tumor microenvironments, since it is systemically toxic.
Illustration of red blood cells, white blood cells and platelets courtesy of Donald Bliss/National Cancer Institute.