中国科学技术大学周荣斌等研究人员合作发现，垂体激素α-MSH促进肿瘤引起的骨髓细胞生成和免疫抑制
研究人员发现，下丘脑-垂体（HP）单元可以促进骨髓造血和免疫抑制，加速肿瘤的生长。皮下植入肿瘤诱发小鼠下丘脑激活和垂体α-MSH（α-MSH）分泌。α-MSH通过其受体MC5R作用于骨髓祖细胞，促进骨髓细胞生成、骨髓细胞聚集、免疫抑制和肿瘤生长。MC5R肽拮抗剂促进了抗肿瘤免疫和抗程序化细胞死亡蛋白1（anti-PD-1）免疫疗法。癌症患者的血清α-MSH浓度升高，并与循环的骨髓源性抑制细胞（MDSC）相关。这些结果揭示了一种抑制肿瘤免疫的神经内分泌途径，并建议将MC5R作为癌症免疫疗法的潜在靶标。
据悉，HP单元可以产生各种激素来调节免疫反应，其下游的一些激素或效应物在癌症患者中会升高。
附：英文原文
Title: Pituitary hormone α-MSH promotes tumor-induced myelopoiesis and immunosuppression
Author: Yueli Xu, Jiaxian Yan, Ye Tao, Xiaojun Qian, Chi Zhang, Libei Yin, Pengying Gu, Yehai Liu, Yueyin Pan, Renhong Tang, Wei Jiang, Rongbin Zhou
Issue&Volume: 2022-08-04
Abstract: 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.
DOI: abj2674
Source: https://www.science.org/doi/10.1126/science.abj2674