Investigating how B cells and antibodies in immune system respond to breast cancer

King’s College London

New research aims to understand how B cells react to the presence of breast cancer.

antibodies

There are important gaps in the knowledge about how our immune system recognises cancer. New research, published in Cancer Research, shows that taking into consideration certain aspects of B cell responses may offer new opportunities to stratify and treat breast cancer more effectively.

The study, led by Professor Sophia Karagiannis, Professor Andrew Tutt and Dr Anita Grigoriadis from the School of Basic and Medical Biosciences and School of Cancer & Pharmaceutical Sciences at King’s and supported by Breast Cancer Now and Cancer Research UK, investigated B cells in the blood and cancer tissues of patients with breast cancer.

Antibodies produced by B cells protect the body from infections by recognising and neutralising pathogens. Antibodies can come in different varieties, known as isotypes, and work to activate the body’s immune system in order to kill the infectious pathogen. The study aimed to understand how this process is involved in breast cancers of different subtypes.

Focusing on the B cell subsets that produce the most active antibodies, which have a stronger advantage of waking up the body’s immune system, the researchers found an active and growing B cell and antibody response profile, especially associated with immunogenic triple-negative breast cancer (TNBC). These B cells carry specific features suggesting that they are distinct to those B cells found in the blood. In the tumours, B cells gather in groups, associate with other immune cells such as T cells, and express types of antibodies which are known to be able to activate the immune system. The research team found that the presence of this active B cell compartment may indicate more favourable patient outcomes.

Despite the poorer prognosis and aggressive nature of TNBC in many, our analyses implicate considerable biological and associated prognostic heterogeneity that extends to the cancer lesion.– Professor Sophia Karagiannis, School of Basic and Medical Biosciences and School of Cancer & Pharmaceutical Sciences (Breast Cancer Now Unit)

Professor Karagiannis continued: “Expanding and active B cells infiltrating cancer lesions in a proportion of individuals could provide a degree of anti-tumour activity that may, in combination with other immune responses, confer a survival benefit and may be exploited with immunotherapies to aid in tumour clearance.”

More research needs to be conducted to better understand how these responses may be linked to patient outcomes. The evaluations observed need to be expanded to large cohorts of patients in order to better understand the precise role and clinical significance of these cells and their expressed antibodies, and how they crosstalk with cancer cells.

Elucidating the microenvironmental conditions required to initiate, sustain and enhance these beneficial anti-tumour responses may be key to developing novel treatments in future.– Professor Sophia Karagiannis, School of Basic and Medical Biosciences and School of Cancer & Pharmaceutical Sciences (Breast Cancer Now Unit)

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