Immune checkpoint inhibitor therapies induce metabolic dysfunction. A study by Wu et al now pinpoints macrophage programmed cell death protein 1 (PD-1) as a key molecular mediator of the anti-PD-1 treatment-triggered exacerbation of systemic metabolic disorders. Macrophage PD-1 blockade disrupts the moonlighting function of PD-1 in suppressing endoplasmic reticulum stress-mediated inflammatory responses, thereby impairing adipose tissue thermogenesis, reducing energy expenditure, and ultimately leading to systemic metabolic dysfunction.
Song et al. (2026) studied this question.