Research published today in Structure has shed new light on how some cancers evade the immune system. The findings have significant implications for the burgeoning field of cancer immunotherapy, an approach that is focused on harnessing the power of our own immune system to eradicate cancer.
“The immune system is complex and highly regulated, comprising a number of accelerators and brakes,” explains Dr. Rich Berry of Monash University. “While the accelerators activate the immune system, the brakes are critical to maintain the balance and prevent the immune system attacking the body's own healthy tissues.”
However, many tumors exploit this mechanism by expressing markers on their surface that engage the brakes, restricting the immune system.
“One method of immunotherapy, termed ‘checkpoint inhibition,’ involves blocking the immune brakes in order to unleash the formidable power of the immune system on the tumor,” Berry says.
So far, two such brakes, PD-1 and CTLA-4, have been effectively targeted in the clinic. However, despite some positive results, many patients do not respond to these treatments. Scientists are on the hunt for new immune brakes to target.
Using high-intensity x-rays at the state-of-the-art Australian Synchrotron, the team from Monash determined the 3D structure of a new immune brake: CD96. The structure reveals the precise molecular details of how CD96 binds to tumors.
“This is really exciting because studies using mouse models indicate that blocking CD96 might be even more effective at controlling tumor spread than the currently available treatments,” says Berry.
These studies could pave the way for future experiments aimed at further interrogating the role of CD96 in tumor control, and ultimately aid in the development of novel agents for the treatment of a range of cancers.