ArticleFrontiers in pharmacology2024
Integrated analysis of single-cell and bulk transcriptome reveals hypoxia-induced immunosuppressive microenvironment to predict immunotherapy response in high-grade serous ovarian cancer.
Article in Frontiers in pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Patient-derived model capturing hypoxia and extracellular matrix remodelling of immunologically cold high-grade serous tumours.Nature communications · 2026Article
- TAMs in the Gynecological Tumor Microenvironment: Insights from Cross-Cancer Studies for Immunotherapy.Cancers · 2026Review
- Artificial intelligence-assisted spatial omics-based biomimetic nanoplatform for intelligent and precise intervention in the immunosuppressive core region of ovarian cancer.NPJ precision oncology · 2026Review
- Microbiome modulation as a therapeutic strategy for alcohol-induced gut dysbiosis and associated disorders.Antonie van Leeuwenhoek · 2025Review
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Authors and funding
5 authors.
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Abstract
Background: Hypoxia is significantly associated with cancer progression and treatment outcomes. Nevertheless, the precise molecular mechanisms underlying the hypoxia-induced immunosuppressive microenvironment in high-grade serous ovarian cancer (HGSOC) are still not fully understood. Methods: By analyzing five independent transcriptomic datasets, we investigated the effect of hypoxia on prognosis and tumor microenvironment (TME) in HGSOC. The hypoxia levels and the intercellular communication signaling pathways were studied by using single-cell analysis. Furthermore, the Hypoxia-TME classifier was developed and then validated in the multiple HGSOC datasets. In addition, we also investigated the prognostic significance, genetic variations, signaling pathways, and the potential for immunotherapy benefits in different Hypoxia-TME subgroups. Results: Hypoxia was identified as a crucial risk factor in HGSOC, and strongly correlated with an immunosuppressive microenvironment characterized by alterations in the composition and distribution of immune cells. Single-cell analysis elucidated the heterogeneity inherent within the TME in HGSOC, and demonstrated an association between the hypoxic TME and fibroblasts as well as macrophages. CellChat analysis identified SPP1-CD44 and CXCL12-CXCR4 as the principal signaling axes through which macrophages and fibroblasts interact with T cells, respectively. Moreover, a personalized Hypoxia-TME classifier was constructed and validated through the integration of the hypoxia (18 genes) and TME (7 immune cells) scores. It was observed that patients in the Hypoxia Conclusion: Our study revealed hypoxia-induced immunosuppressive microenvironment, and developed Hypoxia-TME classifier to distinguish the prognosis, immune characteristics, and potential benefits of immunotherapy in HGSOC.
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