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

Objective: 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). Methods: 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. Results: 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 Conclusion: 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.