UCLA researchers identify a method to make tumors susceptible to immune attack

Source: News Medical Life Sciences, June 2022

One powerful way cancer cells defend against tumor-killing immune cells is to load up their cell surface with a protein known as PD-L1. Now a team of UCLA Jonsson Comprehensive Cancer Center researchers led by Roger S. Lo, MD, PhD, has identified a method to degrade tumor cell-surface PD-L1, thereby making tumors susceptible to immune attack. This approach, in combination with existing therapies, could improve treatment responses of metastatic melanoma and other cancers by suppressing resistance to current therapies.

­­Lo and his co-authors published their findings Tuesday in the journal Cancer Discovery.

Lo, a professor of medicine (dermatology) and molecular and medical pharmacology at UCLA’s David Geffen School of Medicine, and the team at his lab first found that tumor cell-surface PD-L1 is destabilized or degraded by a protein named ITCH. By searching a trove of small molecules at a National Institutes of Health library, they found and deployed a small molecule, which they characterized to be an ITCH activator. By activating ITCH, the small molecule degrades tumor cell-surface PD-L1. This small molecule, when used together with an existing therapy, suppresses relapses of melanoma in animal models.