Natural Killer (NK) cells have long been the soldiers of the immune system that prevents the growth and spread of cancers, and subduing this army of cells is one of the key ways that tumors take hold.

Researchers have discovered a protein found in humans that prevents NK cells from doing their job fighting cancer. Importantly the study, published in the prestigious journal Science Signaling, reveals that blocking this protein - with a naturally occurring hormone currently commercially available - turbocharges the immune system to fight off the cancer cells.

The discovery, in preclinical models, means this hormone, called Follistatin, may be a new and highly potent immune-therapeutic drug for the eradication of cancers such as melanoma.

In the paper, the research team studied what are known as 'Natural Killer' cells in the immune system. These NK cells are crucial in protecting against the triggering of cancer and the spread or metastasizing of cancer cells.

One of the key reasons why cancer cells take hold and grow occurs when these NK cells are in some way suppressed. To date the signals that inhibit NK cells have remained largely a mystery.

The scientists found that a protein - called Activin-A - which is found naturally in both healthy human cells and cancer cells, directly disables the NK cell's capacity to halt cancer growth.

Authors showed that NK cells express the type I activin receptor ALK4, which, upon binding to its ligand activin-A, phosphorylated SMAD2/3 to suppress IL-15–mediated NK cell metabolism. Activin-A impaired human and mouse NK cell proliferation and reduced the production of granzyme B to impair tumor killing. Activin-A also induced SMAD2/3 phosphorylation and stimulated NK cells to increase their cell surface expression of several markers of ILC1 cells. 

Importantly, they were able to block Activin-A in preclinical models, using human and mouse NK cell models, with the hormone Follistatin.

According to the senior author, "these findings may open the door to novel immune-therapy drugs which provide a deeper and more durable way to overcome the immune suppression seen in cancer, improving patient outcomes."

https://stke.sciencemag.org/content/12/596/eaat7527

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