Androgen Loss Accelerates Brain Tumour Growth via HPA Axis Activation
A new study published in Nature reveals that androgens play a previously unrecognized tumour-suppressive role in brain cancers, specifically glioblastoma (GBM). Contrary to earlier beliefs that androgens promote tumour progression, researchers found that androgen loss through castration accelerates intracranial tumour growth in mouse models, while delaying extracranial tumour growth. This organ-specific effect is driven by the hyperactivation of the hypothalamus–pituitary–adrenal (HPA) axis. Androgen deprivation triggers neuroinflammatory signalling via IL-1β and TNF, leading to increased serum glucocorticoids. These glucocorticoids cause systemic T cell dysfunction and promote an immunosuppressive tumour microenvironment by acting on myeloid cells. Spatial transcriptomic analysis confirmed that androgen loss enhances inflammasome activation in microglia. Clinical data from male GBM patients supported these findings, showing that testosterone treatment significantly reduced mortality risk. The study highlights distinct neuroinflammatory and neuroendocrine pathways in androgen-deprived settings, challenging existing assumptions about androgen receptor blockade as a therapy for GBM and emphasizing the complex, organ-specific regulation of antitumour immunity.
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Androgen Loss Accelerates Brain Tumour Growth via HPA Axis Activation
A new study published in Nature reveals that androgens play a previously unrecognized tumour-suppressive role in brain cancers, specifically glioblastoma (GBM). Contrary to earlier beliefs that androgens promote tumour progression, researchers found that androgen loss through castration accelerates intracranial tumour growth in mouse models, while delaying extracranial tumour growth. This organ-specific effect is driven by the hyperactivation of the hypothalamus–pituitary–adrenal (HPA) axis. Androgen deprivation triggers neuroinflammatory signalling via IL-1β and TNF, leading to increased serum glucocorticoids. These glucocorticoids cause systemic T cell dysfunction and promote an immunosuppressive tumour microenvironment by acting on myeloid cells. Spatial transcriptomic analysis confirmed that androgen loss enhances inflammasome activation in microglia. Clinical data from male GBM patients supported these findings, showing that testosterone treatment significantly reduced mortality risk. The study highlights distinct neuroinflammatory and neuroendocrine pathways in androgen-deprived settings, challenging existing assumptions about androgen receptor blockade as a therapy for GBM and emphasizing the complex, organ-specific regulation of antitumour immunity.
Nature