LAUSR

The hypothalamic–pituitary (HP) unit can produce various hormones to regulate immune responses, and some of its downstream hormones or effectors are elevated in cancer patients. We show that the HP unit can promote myelopoiesis and immunosuppression to accelerate tumor growth. Subcutaneous implantation of tumors induced hypothalamus activation and pituitary α-melanocyte-stimulating hormone (α-MSH) production in mice. α-MSH acted on bone marrow progenitors to promote myelopoiesis, myeloid cell accumulation, immunosuppression, and tumor growth through its melanocortin receptor MC5R. MC5R peptide antagonist boosted antitumor immunity and anti–programmed cell death protein 1 (anti–PD-1) immunotherapy. Serum α-MSH concentration was elevated and correlated with circulating myeloid-derived suppressor cells in cancer patients. Our results reveal a neuroendocrine pathway that suppresses tumor immunity and suggest MC5R as a potential target for cancer immunotherapy. Description Hormone hampers cancer immunity Cancer immunotherapy has made great progress in recent years, but many tumors do not respond to any of the available immune treatments for reasons that are often unclear. Among other factors, the neuroendocrine system has been emerging as a potential influence on antitumor immune responses. Xu et al. examined the connections between hypothalamic-pituitary signaling and antitumor immunity, focusing on the role of α-melanocyte–stimulating hormone (α-MSH), which is produced by the pituitary gland. α-MSH promoted the accumulation of immunosuppressive cells, and its inhibition helped to suppress tumor growth in mouse models, suggesting it as a potential therapeutic approach. —YN Release of α-melanocyte stimulating hormone from the pituitary gland interferes with antitumor immunity.