Metabolic inflammation, obesity, and cancer.

Obesity is a global health concern, driving metabolic dysfunction and systemic inflammation. Here, we review the current understanding of the mechanisms underlying the impact of obesity in cancer susceptibility, progression, and response to therapy. We first discuss how resident and recruited macrophages adapt to metabolic stress within adipose tissue and the liver, which are metabolic hub tissues. We consider how obesity-driven myeloid reprogramming extends to other myeloid lineages and influences systemic immune function. Within this framework, where myeloid cells play conserved roles across tissues, we discuss cancer and how obesity-imprinted programs modify antitumor immunity irrespective of tumor site. We propose that local metabolic adaptation results in systemic immune consequences that impact tumor development and progression. Viewing cancer through the lens of obesity-related immunometabolic dysfunction may shed light on tissue- and cancer-specific responses and open avenues to improved therapies and management.