Immunometabolic interactions in gynecologic cancers: Mechanisms, biomarkers, and therapeutic implications
Abstract
This narrative review synthesizes current evidence on immunometabolic interactions in gynecologic cancers, with emphasis on their implications for tumor biology, therapeutic response, and global cancer care. Emerging data indicate that systemic metabolic dysfunction is closely integrated with tumor microenvironment immune remodeling. Key features include enhanced glycolysis, nutrient competition, lipid accumulation, and hypoxia, which collectively impair cytotoxic T-cell function, promote immune exhaustion, and support immunosuppressive myeloid phenotypes.Although gynecologic malignancies share common immunometabolic hallmarks, distinct tumor-specific patterns are evident. Cervical cancer is characterized by human papillomavirus-associated metabolic reprogramming and immune checkpoint activation; ovarian cancer demonstrates dependence on lipid metabolism and omental adipose interactions; and endometrial cancer is strongly associated with obesity-driven insulin resistance and endocrine-inflammatory signaling. This review evaluates potential biomarkers and therapeutic strategies, including metformin, statins, and immune checkpoint inhibitor-based combinations, and clearly distinguishes between preclinical findings and clinically established interventions. Current evidence for metabolic targeting remains largely exploratory, with variable degrees of clinical validation across tumor types. In addition, this review highlights implementation challenges in low- and middle-income…
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