Obesity, inflammation, and cancer immunotherapy: The adipose–immune axis as a therapeutic frontier

The escalating global prevalence of obesity has established it as a significant public health crisis, intricately linked to an increased risk of developing and dying from various cancers. This relationship is fundamentally mediated by a state of chronic, low-grade inflammation, driven by the dynamic and complex “adipose–immune axis.” This axis, a convergence of metabolic and immunological signals, profoundly influences the tumor microenvironment, fostering an environment conducive to tumorigenesis and progression. Concurrently, a compelling and often counterintuitive phenomenon known as the “obesity paradox” has emerged, where patients with a high body mass index (BMI) or elevated adipose tissue levels exhibit paradoxically improved clinical outcomes when treated with certain cancer immunotherapies, particularly immune checkpoint inhibitors (ICIs). This review synthesizes the multifaceted role of the adipose–immune axis, from its pro-tumorigenic mechanisms to its potential to prime the immune system for a robust response to ICIs. It explores the cellular and molecular underpinnings of this dual role, arguing for a conceptual shift from the simplistic BMI metric to a more comprehensive “adipose–immune profile” for patient stratification. Furthermore, the report highlights the adipose–immune axis as a fertile ground for novel therapeutic interventions, detailing conventional strategies alongside emerging technologies such as adipose manipulation transplantation and targeted metabolic inhibitors. The analysis concludes that a deeper understanding of this axis is not only crucial for comprehending cancer pathogenesis but also represents a pivotal frontier for developing next-generation, personalized cancer treatments.