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.READ THE ORIGINAL FULL ARTICLE