Loss of testosterone impairs anti-tumor neutrophil function

Area of Science:

• Immunology
• Oncology
• Endocrinology

Background:

• Melanoma incidence and mortality are higher in men, particularly after age 50.
• The role of age- and sex-dependent immune system changes in cancer control is not fully understood.
• Androgen signaling is crucial in male physiology, but its direct impact on immune cell function in cancer is unclear.

Purpose of the Study:

• To investigate the impact of androgen signaling on neutrophil function and melanoma metastasis.
• To determine if testosterone replacement can mitigate increased metastatic burden in a preclinical model.
• To assess the relevance of observed findings in human cancer patients undergoing androgen deprivation therapy.

Main Methods:

• Utilized castrated male mice models of melanoma.
• Assessed neutrophil maturation and function post-castration and after testosterone replacement.
• Examined neutrophil phenotype in prostate cancer patients receiving androgen deprivation therapy.

Main Results:

• Castration impaired neutrophil maturation and function in mice, increasing melanoma metastatic burden.
• Testosterone replacement normalized neutrophil function and reduced tumor burden in castrated mice.
• Similar aberrant neutrophil phenotypes were observed in prostate cancer patients on androgen deprivation therapy.

Conclusions:

• Androgen signaling is critical for normal neutrophil function.
• Impaired neutrophil function due to low androgens contributes to increased melanoma metastasis.
• Findings highlight the clinical relevance of androgen-mediated immune regulation in cancer.