Lipid Metabolism Reprogramming in Diffuse Large B-Cell Lymphoma (DLBCL): Mechanisms and Treatment Strategies

Diffuse large B-cell lymphoma (DLBCL) is a common, aggressive non-Hodgkin lymphoma with significant molecular heterogeneity. This variability arises in part from its distinct molecular subtypes, including germinal center B-cell-like (GCB) DLBCL, activated B-cell-like (ABC) DLBCL, and primary mediastinal B-cell lymphoma (PMBL), which differ markedly in their genetic profiles, signaling pathway activities, and clinical outcomes. Although rituximab-based R-CHOP regimens have significantly improved patient outcomes, around 40% of patients still experience relapsed or refractory disease. DLBCL cells sustain their rapid proliferation through the establishment of an intricate lipid metabolism regulatory network. The interplay between this network, cell death mechanisms (e.g., ferroptosis), and the tumor immune microenvironment (TIME) significantly impacts the malignant progression of the disease and its resistance to treatment. This review summarizes recent advances in understanding the molecular mechanisms and interplay among these processes in DLBCL and discusses the clinical relevance of associated prognostic biomarkers, thus providing new insights into the development of precision therapies.