Cholesterol in Lymphoma and Hematolymphoid Malignancies: Biological Mechanisms, Clinical Associations, and Therapeutic Implications

Cholesterol is increasingly recognized as a regulator of hematolymphoid malignancy biology, by influencing tumor proliferation, immune function, and therapeutic response. This review summarizes current evidence regarding the relationship between cholesterol metabolism and hematologic malignancies, integrating mechanistic studies with retrospective and emerging prospective clinical data. Cholesterol contributes to immune dysfunction by promoting CD8+ T-cell exhaustion within the tumor microenvironment. Clinical studies have reported associations between serum lipid profiles, statin use, and outcomes across multiple hematologic malignancies, although findings remain heterogeneous and are largely derived from retrospective analyses. Preclinical studies demonstrate that statins disrupt cholesterol-dependent signaling and inhibit tumor growth, whereas retrospective clinical studies generally support the safety of statin use and suggest possible therapeutic benefits in some lymphoma subtypes. Clinically, low high-density lipoprotein cholesterol (HDL) has been associated with advanced disease across multiple hematological malignancies. However, prospective, interventional data remain limited. Collectively, this review highlights the possible relationship between cholesterol metabolism and hematologic malignancy biology, with a focus on potential impacts on disease related outcomes.