Obesity paradoxically advances cancer progression while enhancing certain immunotherapies, like anti-PD-1/PD-L1. Bader et al. discovered that obesity-driven factors increase PD-1 on tumor-associated macrophages (TAMs), suppressing anti-tumor responses. Remarkably, anti-PD-1 therapy reverses this metabolic dysfunction, boosting immune checkpoint blockade (ICB) effectiveness by reactivating PD-1+ TAMs.