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下垂体激素α-MSH促进瘤诱导的骨髓形成和免疫抑制

Yueli Xu¹, Jiaxian Yan¹, Ye Tao²

¹Hefei 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.

Science (New York, N.Y.)

|August 4, 2022

概括

神经内分泌系统,特别是下垂体单位,通过促进骨髓形成和免疫抑制来促进瘤的生长. 向黑色皮质素受体5 (MC5R) 途径可以提高癌症免疫治疗的有效性.

科学领域:

神经内分泌学
免疫学
癌症学

背景情况:

脑下垂体轴通过各种激素调节免疫反应.
在癌症患者中观察到某些与HP相关的激素水平升高.
需要进一步阐明HP单元在促进瘤生长和免疫抑制方面的作用.

研究的目的:

研究HP单元在促进瘤生长中的作用.
确定瘤诱导的免疫抑制所涉及的特定神经内分泌途径.
评估向癌症免疫疗法的治疗潜力.

主要方法:

在小鼠中植入瘤以诱导下丘脑激活和垂体激素的产生.
对α- 黑色素刺激激素 (α-MSH) 对骨髓原体和骨髓细胞积累的影响的评估.
评估与抗编程细胞死亡蛋白1 (抗PD-1) 免疫疗法的MC5R抗剂疗效.
在癌症患者中测量血清α-MSH水平和与髓状细胞衍生的抑制细胞的相关性.

主要成果:

在小鼠中,瘤生长刺激了下丘脑激活和垂体α-MSH的产生.
通过MC5R促进骨髓形成,骨髓细胞积累和免疫抑制,加速瘤生长.
增强了抗瘤免疫力和改善了抗PD-1 免疫治疗结果.
在癌症患者中,血清α-MSH水平升高与骨髓系抑制细胞增加相关.

结论:

通过α-MSH和MC5R信号,HP单元驱动骨髓形成和免疫抑制,从而加速瘤的进展.
这种神经内分泌路径代表了瘤免疫逃逸的新机制.
向MC5R提供了一个有前途的策略来增强抗瘤免疫力,并提高当前癌症免疫疗法的疗效.

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