Loss of testosterone impairs anti-tumor neutrophil function

Janet L. Markman, Rebecca A. Porritt, Daiko Wakita, Malcolm E. Lane, Daisy Martinon, Magali Noval Rivas, Michael Luu, Edwin M. Posadas, Timothy R. Crother and Moshe Arditi ()
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Janet L. Markman: Cedars-Sinai Medical Center
Rebecca A. Porritt: Cedars-Sinai Medical Center
Daiko Wakita: Cedars-Sinai Medical Center
Malcolm E. Lane: Cedars-Sinai Medical Center
Daisy Martinon: Cedars-Sinai Medical Center
Magali Noval Rivas: Cedars-Sinai Medical Center
Michael Luu: Cedars-Sinai Medical Center
Edwin M. Posadas: Cedars-Sinai Medical Center
Timothy R. Crother: Cedars-Sinai Medical Center
Moshe Arditi: Cedars-Sinai Medical Center

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-15397-4

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