テストステロンが男性の脳腫瘍増殖を抑制する可能性（NIH-funded study suggests that testosterone suppresses brain tumor growth in males）

2026-05-06 アメリカ国立衛生研究所（NIH）

＜関連情報＞

• https://www.nih.gov/news-events/news-releases/nih-funded-study-suggests-testosterone-suppresses-brain-tumor-growth-males
• https://www.nature.com/articles/s41586-026-10451-5

アンドロゲンの減少は、HPA軸の活性化を介して脳腫瘍の増殖を促進する Androgen loss accelerates brain tumour growth via HPA axis activation

Juyeun Lee,Yoon-Mi Chung,Daniel J. Silver,Yue Hao,Dylan Scott Lykke Harwood,Alyssa Ealy,Amanda M. Serapiglia,Lee Curtin,Julia R. Benedetti,Christine Ann Pittman Ballard,Kamya Lapsley,Andrea Alvarez-Vazquez,Jessica Goldberg,Cathy Li,Sehaj Kaur,Rian Neal,Sabrina Z. Wang,Kristen E. Kay,Josephine Volovetz,Ellen S. Hong,R’ay Fodor,Jakub Jarmula,Michael Nicosia,Joshua B. Rubin,… Justin D. Lathia
Nature  Published:06 May 2026
DOI:https://doi.org/10.1038/s41586-026-10451-5

Abstract

Many cancers, including glioblastoma (GBM), show a male-biased incidence and associated worse outcomes¹. The mechanisms that underlie this sex difference remain unclear but may involve an immune response² that is partly driven by sex hormones such as androgens. Such hormones are thought to suppress antitumour T cell immunity and to promote tumour progression^3,4. However, here we report a previously unreported tumour-suppressive role for androgens in brain tumours. Using mouse models, we demonstrate that androgen loss via castration accelerates intracranial tumour growth, whereas the opposite effect (delayed tumour growth) is observed in extracranial tumours. Similar effects were observed in male patients with GBM, in whom testosterone treatment significantly reduced the risk of death. In male mice with GBM tumours, castration-induced systemic T cell dysfunction driven by increased levels of serum glucocorticoids, which act on myeloid cells to promote an immunosuppressive tumour microenvironment. Mechanistically, hyperactivation of the hypothalamus–pituitary–adrenal axis in castrated mice with GBM is driven by increased neuroinflammatory signalling through IL-1β and TNF. Spatial transcriptomic analysis further revealed that androgen loss enhances inflammasome activation in microglia, which promotes this neuroinflammatory state. Together, our findings demonstrate that brain tumours drive distinct neuroinflammatory and neuroendocrine pathways in the androgen-deprived setting and highlight organ-specific regulation of antitumour immunity.