In men, the incidence of melanoma rises rapidly after age 50, and nearly two thirds of melanoma deaths are male. The immune system is known to play a key role in controlling the growth and spread of malignancies, but whether age- and sex-dependent changes in immune cell function account for this effect remains unknown. Here, we show that in castrated male mice, neutrophil maturation and function are impaired, leading to elevated metastatic burden in two models of melanoma. Replacement of testosterone effectively normalized the tumor burden in castrated male mice. Further, the aberrant neutrophil phenotype was also observed in prostate cancer patients receiving androgen deprivation therapy, highlighting the evolutionary conservation and clinical relevance of the phenotype. Taken together, these results provide a better understanding of the role of androgen signaling in neutrophil function and the impact of this biology on immune control of malignancies.

在男性中，黑色素瘤的发病率在50岁以后迅速上升，黑色素瘤死亡的近三分之二是男性。已知免疫系统在控制恶性肿瘤的生长和扩散中起关键作用，但是免疫细胞功能的年龄和性别依赖性变化是否可以解释这种作用尚不清楚。在这里，我们表明，在去势雄性小鼠中，中性粒细胞的成熟和功能受到损害，导致黑色素瘤的两种模型的转移负担增加。睾丸激素的替代有效地使去势雄性小鼠的肿瘤负担正常化。此外，在接受雄激素剥夺治疗的前列腺癌患者中也观察到异常的中性粒细胞表型，突出了该表型的进化保守性和临床相关性。在一起