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 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 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 (MDSCs) in cancer patients. Our results reveal a neuroendocrine pathway which suppresses tumor immunity, and suggest MC5R as a potential target for cancer immunotherapy.

中文翻译：

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垂体激素α-MSH促进肿瘤诱导的骨髓生成和免疫抑制

下丘脑-垂体 (HP) 单元可以产生各种激素来调节免疫反应，并且其一些下游激素或效应物在癌症患者中升高。我们表明，HP 单位可以促进骨髓生成和免疫抑制以加速肿瘤生长。肿瘤的皮下植入诱导小鼠下丘脑激活和垂体α-黑素细胞刺激素（α-MSH）产生。α-MSH 通过其受体 MC5R 作用于骨髓祖细胞，促进骨髓生成、骨髓细胞积累、免疫抑制和肿瘤生长。MC5R 肽拮抗剂增强抗肿瘤免疫和抗程序性细胞死亡蛋白 1（抗 PD-1）免疫治疗。血清 α-MSH 浓度升高并与癌症患者的循环髓源抑制细胞 (MDSC) 相关。