Harnessing the Immune System's Cancer Killing Ability

A tolerance mechanism that restrains the activity of natural killer (NK) cells was recently discovered in mice.

In a study published in Proceedings of the National Academy of Sciences, a transcription factor called Kruppel-like factor 2 (KFL2) was found to play a critical role in NK cell expansion and survival.

Since NK cells seek out and destroy tumor cells, a technique called NK cell-mediated tumor therapy, which involves the injection of NK cells that clean the blood of cancer cells in leukemia patients, is currently being used clinically. However, the remission is often short lived.

Transcription factor KLF2, is able to limit immature NK cell proliferation, and instructs mature NK cells to move to areas rich in interleukin 15 (IL-15), which is a necessity for their survival.

“This is the same process likely used by cancer cells to avoid destruction by NK cells,” said researcher Eric Sebzda, PhD.

Tumors could avoid the immune cleaning by promoting KLF2 destruction in the NK cell population, resulting in the starvation of IL-15.

Although the increased expression of IL-15 can improve the immune response to fight against tumors, it’s difficult to introduce the cytokine within a tumor microenvironment solely. Additionally, high systemic levels of IL-15 can be toxic.

The recruitment of cells to the tumor microenvironment that transpresent IL-15 could potentially fix this and improve NK cell-mediated cancer therapy; however, the study concluded that further research is needed.