Image by Joshua Stokes
New findings published in PNAS may help scientists improve the efficacy of natural killer (NK) cell therapy for patients with leukemia.
The preclinical research revealed a tolerance mechanism that restrains the activity of NK cells, as well as a potential way to overcome this problem.
Investigators found that a transcription factor, Kruppel-like factor 2 (KFL2), is critical for NK cell expansion and survival.
Specifically, KLF2 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.
“This is the same process likely used by cancer cells to avoid destruction by NK cells,” said study author Eric Sebzda, PhD, of Vanderbilt University Medical Center in Nashville, Tennessee.
In particular, tumors may avoid immune clearance by promoting KLF2 destruction within the NK cell population, thereby starving these cells of IL-15.
Dr Sebzda and his colleagues noted that increased expression of IL-15 can improve immune responses against tumors. Unfortunately, it’s not easy to introduce the cytokine only within a tumor microenvironment, and high systemic levels of IL-15 can be toxic.
Recruiting cells that transpresent IL-15 to the tumor microenvironment may overcome this barrier and therefore improve NK cell-mediated cancer therapy, the investigators said. However, the methodology hasn’t been worked out yet.
“Our paper should encourage this line of inquiry,” Dr Sebzda concluded.
