Androgen loss weakens anti-tumor immunity and accelerates brain tumor growth.

Autor:	Lee J; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Chung YM; Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, FL, USA.; Sylvester Comprehensive Cancer Center, University of Miami., Curtin L; Mayo Clinic, Mathematical NeuroOncology Lab, Precision Neurotherapeutics Innovation Program, Mayo Clinic, AZ, USA.; Department of Neurosurgery, Mayo Clinic, AZ, USA., Silver DJ; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Hao Y; TGen, Translational Genomics Research Institute, Phoenix, AZ, USA., Li C; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Volovetz J; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA., Hong ES; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.; Medical Scientist Training Program, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA., Jarmula J; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Wang SZ; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.; Medical Scientist Training Program, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA., Kay KE; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA., Berens M; Department of Neurosurgery, Mayo Clinic, AZ, USA., Nicosia M; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA., Swanson KR; Sylvester Comprehensive Cancer Center, University of Miami.; Mayo Clinic, Mathematical NeuroOncology Lab, Precision Neurotherapeutics Innovation Program, Mayo Clinic, AZ, USA., Sharifi N; Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, FL, USA., Lathia JD; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.; Medical Scientist Training Program, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.; Rose Ella Burkhardt Brain Tumor Center, Cleveland Clinic, Cleveland, OH, USA.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2024 Mar 29. Date of Electronic Publication: 2024 Mar 29.
DOI:	10.21203/rs.3.rs-4014556/v1
Abstrakt:	Many cancers, including glioblastoma (GBM), have a male-biased sex difference in incidence and outcome. The underlying reasons for this sex bias are unclear but likely involve differences in tumor cell state and immune response. This effect is further amplified by sex hormones, including androgens, which have been shown to inhibit anti-tumor T cell immunity. Here, we show that androgens drive anti-tumor immunity in brain tumors, in contrast to its effect in other tumor types. Upon castration, tumor growth was accelerated with attenuated T cell function in GBM and brain tumor models, but the opposite was observed when tumors were located outside the brain. Activity of the hypothalamus-pituitary-adrenal gland (HPA) axis was increased in castrated mice, particularly in those with brain tumors. Blockade of glucocorticoid receptors reversed the accelerated tumor growth in castrated mice, indicating that the effect of castration was mediated by elevated glucocorticoid signaling. Furthermore, this mechanism was not GBM specific, but brain specific, as hyperactivation of the HPA axis was observed with intracranial implantation of non-GBM tumors in the brain. Together, our findings establish that brain tumors drive distinct endocrine-mediated mechanisms in the androgen-deprived setting and highlight the importance of organ-specific effects on anti-tumor immunity. Competing Interests: Competing interests N.S. is a co-inventor on a Cleveland Clinic patent on HSD3B1. The other authors declare no competing interest.
Databáze:	MEDLINE
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