Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Science. 2022 Sep 2;377(6610):1085-1091. doi: 10.1126/science.abj2674. Epub 2022 Aug 4.
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.
下丘脑-垂体（HP）单元可以产生各种激素来调节免疫反应，其一些下游激素或效应物在癌症患者中升高。我们表明，HP 单元可以促进髓样细胞生成和免疫抑制，从而加速肿瘤生长。肿瘤的皮下植入诱导了小鼠下丘脑的激活和垂体 α-促黑素细胞激素（α-MSH）的产生。α-MSH 通过其黑素皮质素受体 MC5R 作用于骨髓祖细胞，促进髓样细胞生成、髓样细胞积累、免疫抑制和肿瘤生长。MC5R 肽拮抗剂增强了抗肿瘤免疫和抗程序性细胞死亡蛋白 1（抗 PD-1）免疫治疗。癌症患者的血清 α-MSH 浓度升高，并与循环髓源性抑制细胞相关。我们的结果揭示了一种抑制肿瘤免疫的神经内分泌途径，并表明 MC5R 是癌症免疫治疗的潜在靶点。
