J. Clin. Invest. https://doi.org/10.1172/JCI129502 (2019).

Myeloid-derived suppressor cells (MDSCs) blunt effective immune responses against tumors and contribute to tumor progression. In the Journal of Clinical Investigation, Mohammadpour et al. report that β2-adrenergic receptor (β2-AR) signaling in MDSCs contributes to the immunosuppressive tumor environment. Chronic low-grade stress increased release of norepinephrine by sympathetic nerves, increasing MDSC accumulation within tumors. By contrast, β2-AR-deficient MDSCs were less suppressive in vitro and in vivo, as mice harboring β2-AR-deficient MDSCs exhibited better tumor control. β2-AR signaling in MDSCs activates the STAT3 transcription program and enhances expression of arginase-1, PD-L1 and prosurvival molecules, including Bcl-2. This β2-AR-dependent suppression program also appears to be conserved in human MDSCs, suggesting that targeting of this pathway could contribute to antitumor therapies.