Metabolic Reprogramming of B Cells in Cancer: Effects of Altered Energetics.

B cells, an important component of adaptive immunity, play a key role in defense against a variety of infections and diseases including cancer. B cells play a dual role in cancer, contributing to both anti-tumor immunity and tumor progression. Metabolic reprogramming in the TME has a profound impact on B cell dynamics, reshaping their energetic landscape, influencing their differentiation and effector cell functions. These alterations arise from the complex interplay between intrinsic metabolic pathways and extrinsic factors, such as nutrient availability, hypoxic conditions, and tumor-derived signals. In the TME, B cells promote glycolysis over oxidative phosphorylation (OXPHOS) to meet the high energy demands of activation and proliferation. However, this metabolic plasticity is also mimicked by tumors, leading to dysfunctional B cell phenotypes, such as regulatory B cells (Bregs), which suppress anti-tumor immunity. Nutrient deprivation and accumulation of metabolic byproducts, including lactate, further impair B cell-mediated immune responses. This review highlights the complex interaction between B cell metabolism and cancer, emphasizing the effects of altered energetics on B cell function and implications on tumor progression and therapy. Decoding the metabolic vulnerabilities of B cells in the tumor niche can uncover novel therapeutic strategies against cancer.