When Lucy Booth first started looking at blood samples from melanoma patients, she wasn't sure what she'd find. What she discovered could change how doctors decide who gets immunotherapy—and who might be better off with a different approach.
Booth, a PhD student at King's College London, spent months analyzing tiny shifts in two types of white blood cells: B cells, which make antibodies, and T cells, which hunt down and destroy cancer cells. Her research, published in the Journal for ImmunoTherapy of Cancer, found that changes in these cells during the first six weeks of treatment could predict whether patients would survive or struggle.
Melanoma is the fifth most common cancer in the United Kingdom. It's also one of the deadliest forms of skin cancer—but it's highly treatable when caught early. Immunotherapy, which trains the body's own defenses to fight tumors, has transformed outcomes for many patients with advanced disease. The problem? Nearly half of patients don't benefit from it, and some develop serious side effects with no clear way to know who falls into which group.
That's what makes Booth's findings so significant. Her team studied 24 patients with stage 2 to 4 melanoma receiving treatment at Guy's and St. Thomas' NHS Foundation Trust. They also looked at 25 healthy volunteers for comparison. Using a technology called mass cytometry, which can examine many characteristics of individual immune cells all at once, the researchers tracked how B and T cells changed before treatment and at two points during it.
Patients whose cells showed renewed activation and expansion during those first six weeks had better outcomes, including increased survival. Those whose immune systems kept showing immature or poorly functioning B-cell populations during treatment had poorer results. The team also found that certain T-cell subtypes were linked to side effects.
"Studying immune cells from patients' blood samples is much less invasive than biopsies," Booth said. Her supervisor, Professor Sophia Karagiannis, has spent years investigating how B cells and antibody responses factor into melanoma and immunotherapy. This was the first time circulating B and T cells had been studied together at this level of detail in melanoma patients' blood.
The research builds on last year's work by Karagiannis's group, which identified blood-based B cell markers that could help guide safer treatment. Now, the team hopes their findings could lead to routine blood tests that help doctors personalize care—predicting not just who will respond to immunotherapy, but who might need closer monitoring for side effects.
"We're showing how these different cells of the adaptive immune system behave simultaneously and are altered during treatment," Karagiannis said. "In-depth studies of these cells may provide important insights to help address the current clinical challenges in melanoma treatment."
For patients facing difficult treatment decisions, that kind of clarity can't come soon enough.