Department of Pediatrics, Division of Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Department of Biomedical Sciences, Infectious and Immunologic Disease Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Nat Commun. 2020 Mar 31;11(1):1613. doi: 10.1038/s41467-020-15397-4.
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 岁后迅速上升，近三分之二的黑色素瘤死亡病例为男性。众所周知，免疫系统在控制恶性肿瘤的生长和扩散方面起着关键作用，但年龄和性别相关的免疫细胞功能变化是否对此有影响尚不清楚。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损，导致两种黑色素瘤模型中的转移负担增加。睾酮的替代治疗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。总之，这些结果更好地理解了雄激素信号在中性粒细胞功能中的作用，以及这种生物学对恶性肿瘤免疫控制的影响。
