Researchers discover how B cells detect cancer in the body

Scientists have discovered key features of immune B cells that make them successful in fighting tumors, including when cancer has spread to other parts of the body.

In the journal Nature Immunology, researchers described the development of a computational tool to identify these anti-cancer immune cells, which could lead to improved personalized immunotherapies . Currently, most immunotherapies only work for a minority of patients, and researchers are actively working to expand the group of patients who might benefit from them.

Scientists from the Department of Biochemistry at the University of Oxford, the Institute of Cancer Research London and the University of Cambridge took biopsies from patients with breast cancer and used B-cell receptor sequencing to identify genetic variations in B cells.

B cells, like the better known T cells, are part of the immune system, helping the body fight infections and cancer. They produce proteins called antibodies, which stick to harmful substances such as viruses and cancer and recruit other parts of the immune system to destroy them. When a receptor on a B cell recognizes and binds to a cancer cell, the B cell undergoes changes and becomes even more effective at targeting those cancer cells.

Associate Professor Rachel Bashford-Rogers, lead author of the study and Associate Professor in the Department of Biochemistry at the University of Oxford, said: “Using a combination of different genetic techniques, we showed that both B-cell and T-cell immune responses evolve with changes occurring at specific tumor sites in the body. However, some B cell responses were observed across many or all tumor sites, suggesting that they are looking for cancer cells in different places."

"Here we have identified a common and predictable pattern of immune cell surveillance between multiple tumor sites and developed a tool to accurately identify these cells. We show that this also applies to other diseases, including autoimmune conditions, and so this work lays the foundation for prioritization specific antibodies for the treatment of cancer and other diseases."

The researchers found that some unique B cells, which changed their genetic sequence after recognizing and targeting cancer cells, were present in several metastatic tumor sites where the cancer had spread. This means that after recognizing cancer in one area of the body, B cells migrate to hunt cancer in different parts of the body. B cells found in only one tumor site were less likely to change their sequence and did not perform effective cancer surveillance.

The team also found that the B cells present throughout the patients' treatment were those that recognized cancer and changed their genetic sequence, becoming more effective at recognizing cancer.

The researchers used this information to develop a computational tool that predicts which B cells are most likely to successfully detect and target cancer cells.

They believe that using their predictive tool, it will be possible to find the most successful anti-cancer B cells in a patient and artificially develop the antibodies that these B cells naturally create. This can be used as a personalized immunotherapy that boosts the patient's immune system.

Dr Stephen-John Sammut, first author of the study and head of the Cancer Dynamics Group at the Institute of Cancer Research in London and consultant oncologist at the Royal Marsden Hospital NHS Foundation Trust, said: “When cancer spreads to other parts of the body, it is often much more difficult to Our research shows that the immune response to cancer is not limited to where the tumor initially appears - if an immune B cell successfully detects cancer in one part of the body, it will look for similar cancer cells in other parts of the body."

"Currently there are very few immunotherapies that can be used to treat breast cancer. The computational tool we have developed will allow us to isolate and identify the B cells that recognize cancer cells, as well as the antibodies they produce. This will allow us to develop anti-cancer antibodies similar to those produced by B cells, which can then be used as a personalized treatment to boost the immune response against advanced breast cancer."

Description of breast cancer cohorts and review of study design. Source: Nature Immunology (2024). DOI: 10.1038/s41590-024-01821-0

Professor Christian Helin, director general of the Institute of Cancer Research London, added: "Immunotherapies have changed the outlook for different types of cancer, but unfortunately they still only work for a minority of patients. We need to better understand how the immune system protects the body for cancer, and most research so far has focused on the role of T cells—CAR-T cell therapy is the most prominent treatment to emerge from these studies."

"This research provides exciting insight into the role of B cells during cancer growth and spread, and I look forward to seeing this tool used to focus efforts on developing personalized cancer immunotherapies that can work for many more people than most existing immunotherapies."