1. Loss of testosterone impairs anti-tumor neutrophil function.
- Author
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Markman JL, Porritt RA, Wakita D, Lane ME, Martinon D, Noval Rivas M, Luu M, Posadas EM, Crother TR, and Arditi M
- Subjects
- Androgen Antagonists therapeutic use, Androgens, Animals, Antineoplastic Agents pharmacology, Bone Marrow pathology, Bone Marrow Transplantation, Disease Models, Animal, Female, Hormone Replacement Therapy methods, Lung pathology, Male, Melanoma immunology, Melanoma pathology, Melanoma therapy, Mice, Mice, Inbred C57BL, Mice, Knockout, Prostate pathology, Prostatic Neoplasms genetics, Prostatic Neoplasms immunology, Prostatic Neoplasms pathology, Prostatic Neoplasms therapy, Testosterone immunology, Androgen Antagonists pharmacology, Neutrophils immunology, Neutrophils metabolism, Testosterone metabolism
- Abstract
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.
- Published
- 2020
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