ArticleNature communications2025
Perturbing local steroidogenesis to improve breast cancer immunity.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Spatial organization of the TNBC tumor microenvironment: multicellular niches, T-cell bottlenecks, and therapeutic opportunities.Journal of translational medicine · 2026Review
- Cortisol-resistant CAR-NK cells overcome steroid-induced immunosuppression in lung cancer.Signal transduction and targeted therapy · 2026Article
- Posaconazole mitigates α-amanitin-induced liver injury by inhibiting STT3B-mediated glycosylation and cellular uptake.Frontiers in pharmacology · 2026Article
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Authors and funding
13 authors.
Funding
Abstract
Breast cancer, particularly triple-negative breast cancer (TNBC), evades the body's immune defences, in part by cultivating an immunosuppressive tumour microenvironment. Here, we show that suppressing local steroidogenesis can augment anti-tumour immunity against TNBC. Through targeted metabolomics of steroids coupled with immunohistochemistry, we profiled the existence of immunosuppressive steroids in TNBC patient tumours and discerned the steroidogenic activity in immune-infiltrating regions. In mouse, genetic inhibition of immune cell steroidogenesis restricted TNBC tumour progression with a significant reduction in immunosuppressive components such as tumour associated macrophages. Steroidogenesis inhibition appears to bolster anti-tumour immune responses in dendritic and T cells by impeding glucocorticoid signalling. Undertaking metabolic modelling of the single-cell transcriptomics and targeted tumour-steroidomics, we pinpointed the predominant steroidogenic cells. Inhibiting steroidogenesis pharmacologically using a identified drug, posaconazole, curtailed tumour expansion in a humanised TNBC mouse model. This investigation paves the way for targeting steroidogenesis and its signalling pathways in breast cancer affected by immune-steroid maladaptation.
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