Study Sheds New Light on the Abnormal Phenotypes of B Cells in Skin Cancer

A new study that reveals how B cells react to skin cancer cells may open the door to novel treatment strategies.

The King’s College London-led study, which was published today in Nature Communications, suggests that patients’ antibody-producing B cells may not respond appropriately to melanoma, the most aggressive form of skin cancer.

B cells, a type of white blood cell, make antibodies to help fight infections and prevent them. However, little is known about how melanoma causes B cells to respond and why the antibodies they produce are ineffective.

Researchers used advanced technologies to dig into the intricate workings of the antibody immune response in blood and tissues of patients with metastatic cutaneous melanoma. There are significantly fewer mature (memory) B cells in the blood of patients with late-stage secondary melanoma, which typically provide long-term infection protection. As a result, the blood’s antibody-producing B cells may be less able to fight cancer effectively.

The research additionally finds that active B cells collect at the edge of the tumour and accumulate in small groups. These B cells have specific antibody features and react to melanoma by assembling and communicating with other immune cells, such as T cells, and with other immune cells.

In those melanoma lesions where B cells express specific antibody isotypes, for example, IgG which better enacts the immune system, the presence of B cells is related to better patient survival.

The research additionally finds that B cells in patients with metastatic melanoma likewise cause antibodies which to have comparative capabilities to pathogenic antibodies seen in immune system sicknesses, like the acknowledgment of normal non-cancerous cells. These characteristics might keep the immune system from mounting areas of strength to clear melanoma.

First author Dr Silvia Crescioli, from King’s College London, said: “Our research provides a new perspective on the aberrant nature of B cell phenotypes, antibody characteristics and what they recognize 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.”

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. Franca Fraternali of University College London, Dr. Sophia Tsoka of the Department of Informatics in the Faculty of Natural, Mathematical, and Engineering Sciences, colleagues from King’s College London’s Faculty of Life Sciences & Medicine, Mount Sinai Hospital in Toronto, Canada, the University of Surrey, and clinical colleagues from St. John’s Institute of Dermatology, Guy’s and St. Thomas’ NHS Foundation Trust and the NIHR Biomedical Research Centre were all involved in the study