In a first-of-its-kind study by King’s College London, changes in two major types of immune cells in blood have been linked to different survival outcomes for patients with melanoma. Melanoma, the fifth most common cancer in the UK, is one of the deadliest forms of skin cancer, but is highly treatable when caught early.
Melanoma can be treated with surgery, targeted drugs, and immunotherapy, which works by using the body’s own immune system to recognise and destroy cancer cells.
Immunotherapy has transformed outcomes for many patients with advanced disease – but nearly half of patients do not benefit from it and some develop serious side effects. There is currently no reliable way to predict who will benefit from the treatment and who is at risk of harmful side effects.
In the new research, two types of white blood cells were studied – B cells which produce antibodies and T cells which help to destroy cancer cells. The study revealed coordinated changes in immune responses during immunotherapy that correlate with patient outcomes.
Effective immunotherapy treatment was associated with more efficient B and T cell responses. Patients whose cells showed renewed activation and expansion during the first six weeks of treatment, associated with favourable clinical outcomes, including increased survival. Those whose immune system continued to show immature or poorly functioning B cell populations during treatment associated with poorer outcomes.
Those whose B and T cells were less able to trigger anti-cancer responses before treatment associated with poorer survival outcomes after treatment. Certain T cell subtype populations also associated with side effects during treatment.
Large differences in the immune cell levels of patients were also discovered, potentially influencing how patients respond to immunotherapy.
The research team, which included scientists from King’s Faculty of Life Sciences & Medicine and Faculty of Natural, Mathematical & Engineering Sciences, and Queen Mary University of London, analysed these cells in blood samples from melanoma patients before and at two points during treatment. The study involved 24 patients with stage 2-4 melanoma receiving treatment at Guy’s and St Thomas’ NHS Foundation Trust and 25 healthy volunteers.
B and T cells were characterised using mass cytometry, a type of technology which enables researchers to analyse many characteristics of individual immune cells at the same time. This allowed the team to identify distinct and sometimes rare immune cell populations and to track how they changed during treatment. This was the first time circulating B cells and T cells were studied together at this level of detail in blood samples from melanoma patients.
Lead author Lucy Booth, PhD student at St John's Institute of Dermatology, King's College London, said: “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.”
The findings build upon longstanding research into cancer immunology by a King’s research group, led by Professor Sophia Kariagiannis. Last year, the group identified blood-based B cell markers that could guide safer treatment for patients receiving immunotherapy .
"Over several years, our research has revealed important roles for B cells and antibody responses in melanoma and in immunotherapy. In this study, by analysing 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.", said co-author Professor Sophia Karagiannis, Professor of Translational Cancer Immunology and Immunotherapy at King’s College London.
The latest study, supported by the King’s Health Partners Centre for Translational Medicine, highlights the potential for a more personalised approach to melanoma care. 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.
Lucy Booth added: “We now aim to support more analysis of patient immune cells into clinical settings to guide surveillance and early intervention for melanoma.”
The scientists also plan to investigate B and T cells within tumours themselves to further understand how these white blood cells can 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.
This research was published in the Journal for ImmunoTherapy of Cancer.
Notes to editors
Funding
This study was supported by the British Skin Foundation, the Medical Research Council, MRC Doctoral Training Partnership in Biomedical Sciences, Worldwide Cancer Research, the Royal Society, the CRUK City of London Centre Award, Guy’s and St Thomas’s Foundation Trust Charity Melanoma Special Fund (573), the King’s Health Partners Centre for Translational Medicine, Barts Charity, and the Wellcome Trust.
Journal for ImmunoTherapy of Cancer
Experimental study
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Circulating B cell and T cell activation states predict clinical outcomes in melanoma and reveal dynamic immune reinvigoration with checkpoint inhibitor immunotherapy