Susanna Fletcher Greer, Chief Scientific Officer at the V Foundation, shared a post on LinkedIn about a recent article by Navneet S. Majhail et al, adding:
“Immune therapies have transformed the outlook for people with advanced melanoma. Many patients who once had only months now live for years, and some remain cancer free long after treatment. These treatments give the immune system clearer instructions on how to find and attack melanoma cells, and for many people, the results can be life changing.
But not every melanoma stays quiet. In some cases, the cancer returns after an initial response. A natural question researchers have been asking is: why does this happen and how we can keep treatments working longer? A new study supported by the V Foundation helps answer both parts of that question.
V Grantee Dr. Roger Lo and his team at UCLA looked at melanoma tumors before immunotherapy and again if they came back later. They learned that the cancer is not simply returning in the same form. Rather, cancer is returning with new survival skills that help it slip past the immune system.
One important survival skill involves a process that healthy cells do naturally: when a non-cancerous cell is damaged beyond repair, the cell has an internal process that allows it to shut itself down. In fact, the immune system often relies on this process to help remove dangerous or unhealthy cells (like those infected by viruses).
The surprising finding in this study is that some melanoma cells learn to interfere with that natural shutdown process.
Think of the interference like a building that has quietly disabled its own fire alarm and sprinkler systems. In the case of a fire, the danger could is still present, but the system that should respond is muted. In some melanomas, that internal safety feature, the immune system, has a much harder time finishing the job of killing the cell.
Even more interesting, the Lo team discovered that small pockets of these ‘harder to kill’ cells sometimes exist in a tumor before treatment ever begins. Under the pressure of immune therapy, those pockets can grow and eventually take over. Wowzers.
Here is the hopeful part: once the team understood how the cancer was protecting itself, they began testing ways to reverse that protection. And, in both lab studies and mouse models, drugs that restored the cell’s ability to respond to danger signals made immunotherapy effective again. In some situations, combining these medicines with immunotherapy helped prevent resistance from forming at all. Super cool!
This is powerful progress. It gives us a clearer picture of why relapse happens and a hopeful path toward keeping immunotherapy working longer for more patients. It also shows exactly why investing in fundamental discovery research matters: every new insight brings us closer to treatments that stay a step ahead of cancer.
Find the Lo Lab at Roger Lo Lab – Dermatology | UCLA Health and read this awesome paper at Genomic copy-number variants drive apoptotic evasion underlying acquired resistance to immune checkpoint inhibitors: Immunity.”
Title: Genomic copy-number variants drive apoptotic evasion underlying acquired resistance to immune checkpoint inhibitors
Authors: Navneet S. Majhail, Tonya Cox, Stephanie Larson, Minoo Battiwalla, Aravind Ramakrishnan, Paul Shaughnessy, Michael Tees, Nicole Zahradka, Matt Wilkes, Jeremy Pantin
Read the Full Article on Immunity
More posts featuring Susanna Fletcher Greer.