Cancer drugs known as immune checkpoint inhibitors unleash the body’s immune cells to attack tumors. And for some patients in whom the drugs seemingly fail, there actually is an immune response — it’s just not powerful enough to kill off cancer cells. Researchers have found a new way to predict which patients will have a response, however small, and hope it’ll give clinicians a way to strike while the iron is hot with combination therapies that might improve outcomes. Here’s what microbiologist John Wherry of the University of Pennsylvania said about the work, published in Nature.
How did you study the gap between activating those immune cells and seeing an actual clinical effect?
We wanted to use peripheral blood, just blood circulating through the body, as a way to understand what’s happening in the immune system. We were looking for a specific type of T cell that we suspect is activated by the drugs. And by looking for them, we could identify which patients were and weren’t responding clinically. We determined that in patients that have small tumors, the body doesn’t need a very large amount of immune change to have effect. In patients with larger tumors or more metastases, what the drug is asking the immune system to do is substantially greater. That tells us the immune system is calibrated to the amount of disease.
How can you use that information?
So we took that information and determined a ratio that is able to predict who is going to respond and who is not. It gives us an early measure to look at the effect of drugs that patients have just started taking. And for patients with a less powerful response, it gives us an opportunity to come in with additional therapies when their response to the [checkpoint inhibitor] drugs is at its highest.