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Research Article: Phenotypic, functional and metabolic features of B cells from a small cohort of breast cancer patients

Date Published: 2026-09-25

Abstract:
Identify and characterize breast cancer (BC)-induced changes of humoral immunity and B cell function in a small cohort of treatment-naïve breast cancer patients (BCPs) as compared to healthy controls (HCs). The peripheral blood from newly diagnosed, treatment-naive breast cancer patients (BCPs) and age-matched cancer-free individuals (HCs) was collected. B cells were isolated and cellular, molecular, functional and metabolic analyses were performed. There is a redistribution of B cell subsets in the blood of BCPs versus HCs with increased frequencies of pro-inflammatory B cell subsets in BCPs. B cells from BCPs secrete higher amounts of pro-inflammatory cytokines than B cells from HCs, due to the activation of the transcription factor NF-kB. B cells from BCPs also secrete high amounts of the metabolite lactate and are highly glycolytic, as shown in a Seahorse mitostress test. This hyper-metabolic phenotype can be inhibited at least in vitro by blocking lactate transport. Results have identified a set of distinct and significant changes in the circulating B cells of our cohort of BCPs that may help to establish a baseline B cell signature of BCPs before therapy, to predict B cell performance during therapy by identifying immunosuppressive cells, and to design precision therapeutic approaches.

Introduction:
Breast cancer (BC) is the most frequently diagnosed malignancy in women worldwide ( 1 ). In 2025, an estimate of >300,000 new cases of invasive BC have been diagnosed in the U.S., making it the most common non-skin cancer accounting for almost 30% of all new cancer diagnoses in females ( https://www.nationalbreastcancer.org/breast-cancer-facts/ ). Our ongoing studies and those by several other groups have revealed that BC starts to adversely change the patient’s immune system from early on in its development…

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