A new study from King's College London has identified specific patterns in white blood cells that can predict treatment outcomes for melanoma patients receiving immunotherapy. The research analyzed two major types of immune cells in blood samples and found that coordinated changes in these cells during the first six weeks of treatment correlate strongly with patient survival and risk of side effects.

Why This Matters for Melanoma Patients?

Melanoma is the fifth most common cancer in the UK and one of the deadliest forms of skin cancer, though it is highly treatable when caught early. Immunotherapy has transformed outcomes for many patients with advanced disease by harnessing the body's own immune system to recognize and destroy cancer cells. However, nearly half of patients do not benefit from immunotherapy, and some develop serious side effects. Currently, doctors have no reliable way to predict who will respond well and who is at risk of harm.

The new findings could change that. By analyzing blood samples before treatment and at two points during the first six weeks, researchers identified distinct immune cell populations that signal treatment success or failure. This less invasive approach using blood samples offers a major advantage over traditional tissue biopsies.

What Did the Research Reveal About Immune Cells?

The study examined two types of white blood cells: B cells, which produce antibodies, and T cells, which help destroy cancer cells. Researchers analyzed blood samples from 24 patients with stage 2-4 melanoma and 25 healthy volunteers using mass cytometry, a technology that allows scientists to analyze many characteristics of individual immune cells simultaneously.

The findings revealed clear patterns that predict outcomes:

• Successful Treatment Response: Patients whose B and T cells showed renewed activation and expansion during the first six weeks of treatment had favorable clinical outcomes, including increased survival rates.
• Poor Treatment Response: Patients whose immune systems continued to show immature or poorly functioning B cell populations during treatment experienced poorer outcomes and lower survival rates.
• Pre-Treatment Indicators: Those whose B and T cells were less able to trigger anti-cancer responses before treatment even began had poorer survival outcomes after treatment started.
• Side Effect Risk: Certain T cell subtype populations were associated with serious side effects during treatment, allowing doctors to identify at-risk patients early.

"B cells have emerged as critical contributors to survival and treatment outcomes in melanoma. In-depth studies of these cells may provide important insights to help address the current clinical challenges in melanoma treatment. Studying immune cells from patient blood samples allows for a much less invasive method than biopsies," said Lucy Booth, a PhD student at St John's Institute of Dermatology at King's College London.

Lucy Booth, PhD Student, St John's Institute of Dermatology, King's College London

The research team also discovered large differences in immune cell levels among patients, suggesting that individual variation in immune function significantly influences how people respond to immunotherapy.

How Could This Change Melanoma Treatment?

The findings build on previous research by the same team at King's College London. Last year, the group identified blood-based B cell markers that could guide safer treatment for patients receiving immunotherapy. This latest study goes further by analyzing both B cells and T cells together over time, showing how these different cells of the adaptive immune system behave and change during treatment.

"Over several years, our research has revealed important roles for B cells and antibody responses in melanoma and in immunotherapy. In this study, by analyzing both B cells and T cells together over time, we show how these different cells of the adaptive immune system simultaneously behave and are altered during treatment," explained Professor Sophia Karagiannis, Professor of Translational Cancer Immunology and Immunotherapy at King's College London.

Professor Sophia Karagiannis, Professor of Translational Cancer Immunology and Immunotherapy, King's College London

In the future, blood-based immune profiling could help identify patients most likely to benefit from immunotherapy, those at greater risk of side effects, and patients who may require closer monitoring during treatment. The researchers plan to support more analysis of patient immune cells in clinical settings to guide surveillance and early intervention for melanoma.

What's Next for Melanoma Research?

The scientists also plan to investigate B and T cells within tumors themselves to further understand how these white blood cells impact patient outcomes. For future research, the academics suggest replicating the study in a larger cohort or in other cancers, such as triple negative breast cancer, which has limited treatment options.

Meanwhile, the field of melanoma treatment continues to advance. The FDA recently granted accelerated approval to Tudriqev, a novel oncolytic viral therapy based on the herpes simplex virus, for patients with advanced melanoma that no longer responds to standard immunotherapy. This therapy is injected directly into tumors and works by destroying cancer cells from the inside while stimulating the immune system to attack remaining tumor cells. In clinical trials, 24% of patients experienced tumor shrinkage, with some responding for more than a year.

Additionally, the Melanoma Research Alliance has launched a new Melanoma Biorepository to help researchers access patient tissue samples for studying rare melanoma subtypes like acral and mucosal melanoma. Patients can donate tissue samples, blood, or cheek swabs to support research that may lead to better diagnostic approaches and new treatments.

These developments represent a shift toward more personalized melanoma care, where blood tests and immune profiling could help doctors tailor treatment decisions to individual patients' immune profiles, potentially improving outcomes and reducing unnecessary side effects.