Ученые создали детальную карту развития B-клеток в меланоме для поиска новых биомаркеров

Researchers have created one of the most detailed maps to date of how white blood cells called B cells develop and behave inside melanoma tumours, a type of skin cancer. The study, led by King's College London and published in the Journal of Experimental & Clinical Cancer Research, provides new insights into how B cells develop, organise and interact within the melanoma tumour microenvironment before and after immunotherapy. There are currently no reliable biomarkers to predict which patients with melanoma will respond to immunotherapy. The researchers hope their findings could contribute to the development of future biomarkers to help guide treatment decisions and improve outcomes for patients. B cells are the immune cells that make antibodies. They are commonly found in both primary and advanced melanoma. B cells develop and change over time and are often found alongside other immune cells in specialised immune hubs within tumours called tertiary lymphoid structures. However, many aspects of their development, location and function within melanoma, and how they influence responses to immunotherapy, have remained unclear. The research team combined advanced technologies to create a detailed picture of how B cells develop, communicate with other immune cells and produce antibodies within melanoma tumours. They analysed blood and tumour samples from patients treated at Guy's and St Thomas' NHS Foundation Trust, alongside external datasets to validate their findings. The team identified a previously unrecognised "inflamed" or activated B cell state, where the behaviour of the B cells was controlled by signalling proteins called interferons. These activated B cells persisted throughout disease progression and after immunotherapy. They were consistently found across patients, often located near other key immune cells, and clustered in specialised regions of tumours where the immune system coordinates long-term immune responses. The researchers saw that the B cells changed and developed within tumours over time, moving from immature cells into more specialised types, such as the activated B cell state. The researchers also observed differences between the B cells found in patients who responded to immunotherapy and those who did not, suggesting that tumours from responders and non-responders may have distinct B cell profiles. Tumours from responders were more likely to contain B cell populations linked with organised immune responses within the tumour. However, the researchers emphasise that larger studies are needed to confirm these findings and to determine whether B cells play a role in treatment response. The study also showed that melanoma tumours contain B cells that produce different types of antibodies, and that B cell responses continued to evolve even after immunotherapy treatment. Professor Sophia Karagiannis, Professor of Translational Cancer Immunology and Immunotherapy at King's College London and co-senior author of the study, said: "B cells are emerging as important contributors to anti-tumour immunity. In this study, we were able to follow B cells through their developmental journeys within melanoma tumours and reveal how they organise into specialised immune structures, communicate with other immune cells and produce distinct antibody responses. These findings provide one of the most detailed pictures to date of B cell behaviour in melanoma and highlight the remarkable complexity of immune activity within the tumour microenvironment." Importantly, we identified previously underappreciated B cell states that persist through disease progression and after immunotherapy. While further work is needed to understand their precise biological roles, our findings provide new clues about how the immune system adapts within tumours and how different immune programmes may shape patient outcomes. Professor Sophia Karagiannis, Professor of Translational Cancer Immunology and Immunotherapy at King's College London and co-senior author of the study The team was made up of scientists from the Faculty of Life Sciences & Medicine and the Faculty of Natural, Mathematical & Engineering Sciences at King's College London, as well as the University of Surrey, UCL and Queen Mary University of London. The study highlights the power of interdisciplinary research, bringing together expertise in immune cell biology and bioinformatics to reveal new insights into how B cells behave within melanoma tumours. As no single data set and analytical approach can capture the full complexity of the tumour immune environment, integrative modelling is essential. With bulk sequencing (where all cells in a sample are sequenced), single-cell, spatial transcriptomic and antibody sequencing data, we can connect the average molecular signal with the cell types and states present, their location within the tumour and map out how B cells evolve. In this study, integrating these complementary layers transformed fragmented observations into a coherent biological picture, to reveal the different routes by which B cells develop in cancer and their relationship to clinical outcomes. Dr Sophia Tsoka, Reader in Bioinformatics at King's College London and co-senior author of the paper Advancing research is essential to improving outcomes for everyone affected by skin disease and skin cancer. At the British Skin Foundation, we are proud to fund research that deepens scientific understanding, inspires innovation, and helps shape the future of diagnosis, treatment and care. Together, these advances bring us closer to a future with better outcomes for patients and their loved ones. Matthew Patey OBE, Chief Executive, British Skin Foundation The study was supported by the British Skin Foundation, the Medical Research Council, Worldwide Cancer Research, the Royal Society, Cancer Research UK City of London Centre, Guy's Cancer Charity, Barts Charity, Wellcome and King's Health Partners Centre for Translational Medicine.