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09 June 2023

Study uncovers how B cells react to skin cancer

A new study that sheds light on how B cells react to skin cancer cells could pave the way for innovative therapy design.

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The study, published today in Nature Communications and led by researchers from King’s, reveals that antibody-producing B cells in patients may be defective in responding to the most aggressive skin cancer, melanoma.

Antibodies are produced by B cells, a type of white blood cell, and are made to prevent and help fight infections. However, there is limited understanding about how B cells are prompted to respond to melanoma and why the antibodies they make are not effective.

Researchers used advanced technologies to delve into the intricate workings of the antibody immune response in blood and tissues of patients with metastatic cutaneous melanoma. The blood of patients with late-stage secondary melanoma shows significantly lower levels of mature (memory) B cells, which normally provide long-term protection from infections. This means that the antibody-producing B cells in the blood may be less able to mount effective responses against cancer.

Lead author Professor Sophia Karagiannis from St John’s Institute of Dermatology, School of Basic and Medical Biosciences, said: “The findings of this study offer a deeper understanding of the intricate immune response deficits involved in metastatic cutaneous melanoma and their potential clinical significance. We are studying B cell signatures in different and larger cohorts of patients to better understand how these deficient antibody responses we have uncovered may be linked to patient outcomes. We are conducting extended research to elucidate how B cells interact with cancer cells and to dissect the conditions that initiate and enhance effective B cell and antibody responses. Together, these will offer opportunities for innovative therapy design in future.”

The research also finds that active B cells accumulate at the edge of the tumour and gather in small groups. These B cells carry specific antibody features and react to melanoma by assembling and communicating with each other, and with another immune cell type known as T cells.

In those melanoma lesions where B cells express specific antibody isotypes, such as IgG which better activates the immune system, the presence of B cells is associated with more favourable patient survival.

The research also finds that B cells in patients with metastatic melanoma also make antibodies which have similar functions to pathogenic antibodies seen in autoimmune diseases, such as the recognition of normal non-cancerous cells. These characteristics may prevent the immune system from mounting a strong response to clear melanoma.

Our research provides a new perspective on the aberrant nature of B cell phenotypes, antibody characteristics and what they recognise in metastatic cutaneous melanoma. By uncovering autoimmune signatures and the highly active, yet abnormal, B cell response in the tumour microenvironment, we open doors to specific treatment advancements.

First author Dr Silvia Crescioli, from St John’s Institute of Dermatology, School of Basic and Medical Biosciences

Dr Joseph Ng, from University College London, co-author of the study said: 'Through analysing large datasets of B cell and antibody profiles found in melanoma, we can gather in-depth knowledge of the types of responses that may offer anti-tumour benefit, and this could provide clues for the development of novel treatments.”

Dr Katie Lacy, a Visiting Reader in Dermato-Oncology at King's said: "Despite the significant advances in the treatment of advanced melanoma, there remains an unmet need to develop more effective treatments in addition to identifying bio markers to monitor for disease recurrence and response to treatment. To date therapeutic strategies have focused on targeting the T cell compartment. This study provides valuable insights into B cell responses in melanoma, demonstrating an important role for this part of the immune system. Further understanding of the B cell responses will hopefully guide optimisation of therapy and monitoring of patients with melanoma in the future."

The study was conducted in close collaboration with Dr Franca Fraternali at University College London, Dr Sophia Tsoka at the Department of Informatics, Faculty of Natural, Mathematical and Engineering Sciences, colleagues across the Faculty of Life Sciences & Medicine, King’s College London, Mount Sinai Hospital, Toronto, Canada, University of Surrey and with clinical colleagues at St John's Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust and the NIHR Biomedical Research Centre.

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Sophia Karagiannis

Professor of Translational Cancer Immunology and Immunotherapy