ArticleThe Journal of clinical investigation2023
Tumors produce glucocorticoids by metabolite recycling, not synthesis, and activate Tregs to promote growth.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 39 citations in OpenAlex.
- Lipid-Soluble Signaling Molecular Model Predicts Prognosis and Immunotherapy Response in Gastric Cancer.Lipids · 2026Article
- Signaling Under Stress: Targeting the Glucocorticoid Receptor in Cancer.Cancer research · 2026Review
- Depression remodels tumor microenvironment to drive tumor progression: Bio-behavioural signalling pathways and clinical interventions.Journal of advanced research · 2026Review
- Endogenous glucocorticoids and glucocorticoid receptor signaling: Dual regulators of PD-1/PD-L1 immunotherapy efficacy in the tumor microenvironment.Chinese medical journal · 2026Review
- Integral Lipophilicity Studies with in Silico ADMET Parameter Analysis of Novel Pseudothiohydantoin Derivatives.International journal of molecular sciences · 2026Article
- Chronic stress unleashes an intratumor phage-fibroblast-B cell circuit to promote tumor growth.Cancer cell · 2026Article
- Chronic stress and cancer progression through neuro‑endocrine‑immune networks (Review).Oncology reports · 2026Review
- Glucocorticoids induce a phagocytic C1Q+ macrophage phenotype primed for IFNγ-dependent CXCL9 secretion.Scientific reports · 2026Article
- Fibroblast-derived HSD11B1 deficiency drives lung cancer in never-smokers through steroid metabolic imbalance.NPJ precision oncology · 2026Article
- Cortisol-resistant CAR-NK cells overcome steroid-induced immunosuppression in lung cancer.Signal transduction and targeted therapy · 2026Article
- Dexamethasone promotes neutrophil ROS-mediated tumor killing through the glucocorticoid receptor.Oncogene · 2026Article
- Selective Glucocorticoid Receptor Modulators of Immune Checkpoint Function.bioRxiv : the preprint server for biology · 2026Article
- Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis.Signal transduction and targeted therapy · 2026Review
- Glucocorticoid Receptor Activation Reprograms NK Cells to Drive AREG-Mediated Immunosuppression: A Pan-Cancer Role for AREG.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Baseline serum cortisol as a prognostic biomarker for immune checkpoint inhibitor therapy in advanced gastric cancer.Frontiers in oncology · 2026Article
- The parental intestinal microbiome modulates systemic and local glucocorticoid levels in neonatal mice.PloS one · 2026Article
- Stress Biology in Cancer: Neuroendocrine-Immune Mechanisms Linking Tumor Progression to Translational Interventions.Cancer communications (London, England) · 2026Review
- The role of hormonal and nutritional biomarkers in predicting immune checkpoint inhibitor efficacy: current limitations and future prospects.Frontiers in immunology · 2026Review
- Impact of steroid differentiation on tumor microenvironment revealed by single-nucleus atlas of adrenal tumors.Nature communications · 2025Article
- Urinary Metabolites and Survival in Malignant Mesothelioma.medRxiv : the preprint server for health sciences · 2025Article
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7 authors at 2 institutions in 2 countries.
Funding
Abstract
Glucocorticoids are steroid hormones with potent immunosuppressive properties. Their primary source is the adrenals, where they are generated via de novo synthesis from cholesterol. In addition, many tissues have a recycling pathway in which glucocorticoids are regenerated from inactive metabolites by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1, encoded by Hsd11b1). Here, we find that multiple tumor types express Hsd11b1 and produce active glucocorticoids. Genetic ablation of Hsd11b1 in such cells had no effect on in vitro growth, but reduced in vivo tumor progression, which corresponded with increased frequencies of CD8+ tumor-infiltrating lymphocytes (TILs) expressing activation markers and producing effector cytokines. Tumor-derived glucocorticoids were found to promote signatures of Treg activation and suppress signatures of conventional T cell activation in tumor-infiltrating Tregs. Indeed, CD8+ T cell activation was restored and tumor growth reduced in mice with Treg-specific glucocorticoid receptor deficiency. Importantly, pharmacologic inhibition of 11β-HSD1 reduced tumor growth to the same degree as gene knockout and rendered immunotherapy-resistant tumors susceptible to PD-1 blockade. Given that HSD11B1 expression is upregulated in many human tumors and that inhibition of 11β-HSD1 is well tolerated in clinical studies, these data suggest that targeting 11β-HSD1 may be a beneficial adjunct in cancer therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.