Obesity and Cancer: From Systemic Metabolic Reprogramming to Immunotherapy Paradox

With the global rise in overweight and obesity, excess adiposity has emerged as a modifiable carcinogenic exposure. Beyond energy surplus, obesity establishes a durable pro-tumorigenic baseline through endocrine-metabolic rewiring, chronic low-grade inflammation, and structural/mechanical remodeling of tissues, thereby shaping organ-specific microenvironments that favor malignant transformation and progression. This review integrates systemic metabolic and endocrine alterations with tumor microenvironmental physical barriers, immune reprogramming, and neuroimmune regulation to explain heterogeneity in cancer risk, progression, and treatment response. We propose a stratified assessment framework based on measurable indicators-body composition, inflammatory status, and treatment exposure-to support risk prediction, mechanistic validation, and the design of actionable experimental and clinical strategies.