The impact of obesity-related systemic inflammation on the efficacy, toxicity, and biomarkers of immune checkpoint inhibitors in lung cancer: from mechanisms to clinical management

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of lung cancer, yet the heterogeneity in their efficacy and toxicity among different patients remains a significant clinical challenge. Obesity, as a global epidemic associated with chronic low-grade systemic inflammation and complex immunometabolic disturbances, has been identified as a crucial regulatory factor in cancer immunotherapy response. This review aims to systematically and deeply explore the intricate network of interactions between obesity, lung cancer, and immunotherapy. We not only examine the molecular and cellular mechanisms by which obesity-related inflammation influences ICI efficacy through remodeling the tumor microenvironment, altering systemic immune status, and modulating the gut microbiota, but also comprehensively assess its complex impact on clinical outcomes of ICI (including the controversial "obesity paradox" phenomenon) and immune-related adverse events (irAEs), particularly those uniquely associated with endocrine toxicity. Simultaneously, we systematically review novel biomarkers centered around obesity-related inflammatory parameters and body composition (such as circulating adipokines and radiomic features) and their application in integrative predictive models. Finally, based on available evidence, we propose multidisciplinary, longitudinal clinical management strategies tailored for obese lung cancer patients and envision novel combination treatment directions targeting the obesity-inflammation axis, aiming to provide theoretical support and practical guidance for achieving more precise, individualized immunotherapy.