Paradoxically, obesity is a risk factor for cancer but is also associated with a survival advantage in patients treated with immune-checkpoint inhibitors. Macrophage expression of programmed cell death protein 1 (PD1) might link these two findings, according to a new study by Jeffrey Rathmell and colleagues.

In vitro, upregulation of PD1 expression on macrophages depended on inflammation-induced glycolysis; enhanced PD1 had direct effects on the macrophage phenotype as it promoted lipid uptake and metabolism, while inhibiting glycolysis and phagocytosis. Accordingly, in vivo anti-PD1 treatment increased TAM phagocytosis and lowered lipid uptake, with reduced tumour weight even in T cell-depleted mice. Moreover, selective loss of PD1 on macrophages improved T cell activation and proliferation. Overall, despite its protumour effects, obesity-induced PD1 on TAMs might enhance the benefits of targeting PD1 beyond its direct effects on T cells by rewiring macrophages.