Researchers at The Scripps Research Institute (TRSI) are fueling the future of cancer treatment by improving a powerful tool in disease defense: the body's immune system. By revealing a novel but widespread cell signaling process, the scientists may have found a way to manipulate an important component of the immune system into more effectively fighting disease.
The study, recently published online ahead of print by the journal Blood, shows that disabling a particular enzyme, called ItpkB, in mice improves the function of a type of immune cell called Natural Killer cells.
"This is an exciting finding because it could possibly lead to the development of drugs that improve Natural Killer cell function," said TSRI Associate Professor Karsten Sauer, PhD, who led the study. "Natural Killer cells have gained clinical interest as innovative biological therapeutics for certain cancers and also in certain infectious diseases."
The Body's 'SWAT Team'
Natural Killer cells patrol the body and detect characteristic alterations on the surface of cancer cells or virus-infected cells. Through a complicated and little understood signaling machinery—a domino effect of molecular reactions in a cell that ultimately produces a certain signal—Natural Killer cells then destroy such "stressed" cells.
Compared to other types of immune cells, Natural Killer cells kill these cells quickly. This makes Natural Killer cells important early responders of the immune system. Not surprisingly, researchers have explored engaging this "SWAT team" of the body therapeutically, particularly in blood cancers.
However, to date, the therapeutic efficacy of Natural Killer cells has been limited. "A key bottleneck is our limited understanding of signaling mechanisms that dampen Natural Killer cell function," Sauer said.
Sauer and colleagues' new research reveals crucial details of this puzzle.
A Way to Prime the Attack
The Sauer group had previously identified ItpkB as a key regulator of immune function. ItpkB acts primarily by producing IP4, a small molecule messenger that controls the functions of various other important signaling molecules. IP4 can improve or inhibit signaling depending on the cell type in which it is produced.
The new research showed that Natural Killer cells from mice lacking ItpkB show elevated signaling and function better than Natural Killer cells that have the enzyme. As a result, mice lacking ItpkB are more effective than mice expressing ItpkB in attacking cells that display characteristic surface changes of cancer cells.
"The enzyme ItpkB has unique features that facilitate its highly specific inhibition by small molecules," said Sauer. "Our findings suggest that such compounds could possibly be used to improve Natural Killer cell function therapeutically. If successful, this could overcome a bottleneck and engage the body's SWAT team to fight cancer."
Scripps Research Institute: http://www.scripps.edu
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Bumblebees can recall which flowers yield nectar, but like people they can get mixed up – leading them to home in on flowers they have no experience of
Brain cells that help us predict the intentions of others before they've actively made a decision have been discovered in monkeys
Experiments in mice suggest that treatment of haemophilia could be more successful if the baby's immune system is primed while in the womb
Scientists have recovered cultivated wheat DNA from an 8,000-year-old submerged site off the British coast. The finding suggests hunter-gatherers were trading for the grain long before they grew it.
An exciting fossil find in China points to a 525-million year old sea-dweller who used its new backbone to swim nimbly away from predators
Birds are dinosaurs. That’s a fact underscored by dozens upon dozens of discoveries in the last 30 years.
Eyelashes keep dust out and fend off drying breezes, a study finds. To do that they need to be a very precise length. Extra-long fake eyelashes hurt more than they help.
New research from UCL brings us closer to finding out what’s behind one of our biggest killers
The UK has now become the first country to approve laws to allow the creation of babies from three people.
Three people with paralysed arms had their hands amputated and replaced by prosthetic ones that they control with their mind