ArticleInternational journal of molecular sciences2021
Hijacking Sexual Immuno-Privilege in GBM-An Immuno-Evasion Strategy.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Dissecting glioblastoma risk signatures in the tumor immune microenvironment based on multi-dimensional transcriptomics.GigaScience · 2026Article
- Therapeutic targeting of post-translational modifications in ovarian cancer: mechanisms and clinical applications.Journal of ovarian research · 2025Review
- Estrogen Receptors as Key Factors in Carcinogenesis.Biomedicines · 2025Review
- Gender- and Grade-Dependent Activation of Androgen Receptor Signaling in Adult-Type Diffuse Gliomas: Epigenetic Insights from a Retrospective Cohort Study.Biomedicines · 2025Article
- Fast Evolving Glioblastoma in a Pregnant Woman: Diagnostic and Therapeutic Challenges.Diagnostics (Basel, Switzerland) · 2025Article
- Application of bioinformatics analysis to construct the prognostic model and immune-related gene characteristics of low-grade glioma.Discover oncology · 2025Article
- Impact of Sex Hormones on Glioblastoma: Sex-Related Differences and Neuroradiological Insights.Life (Basel, Switzerland) · 2024Review
- Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.Journal of hematology & oncology · 2024Review
- Multi-Omics profiling identifies aldehyde dehydrogenase 2 as a critical mediator in the crosstalk between Treg-mediated immunosuppression microenvironment and hepatocellular carcinoma.International journal of biological sciences · 2024Article
- Macrophages in the Glioblastoma Tumor Microenvironment.International journal of molecular sciences · 2023Article
- Acquisition of Immune Privilege in GBM Tumors: Role of Prostaglandins and Bile Salts.International journal of molecular sciences · 2023Article
- Microglia and Brain Macrophages as Drivers of Glioma Progression.International journal of molecular sciences · 2022Review
- Androgen Receptor Expression in the Various Regions of Resected Glioblastoma Multiforme Tumors and in an In Vitro Model.International journal of molecular sciences · 2022Article
- Allopregnanolone Promotes Migration and Invasion of Human Glioblastoma Cells through the Protein Tyrosine Kinase c-Src Activation.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulatory T-cells (Tregs) are immunosuppressive T-cells, which arrest immune responses to 'Self' tissues. Some immunosuppressive Tregs that recognize seminal epitopes suppress immune responses to the proteins in semen, in both men and women. We postulated that GBMs express reproductive-associated proteins to manipulate reproductive Tregs and to gain immune privilege. We analyzed four GBM transcriptome databases representing ≈900 tumors for hypoxia-responsive Tregs, steroidogenic pathways, and sperm/testicular and placenta-specific genes, stratifying tumors by expression. In silico analysis suggested that the presence of reproductive-associated Tregs in GBM tumors was associated with worse patient outcomes. These tumors have an androgenic signature, express male-specific antigens, and attract reproductive-associated Related Orphan Receptor C (RORC)-Treg immunosuppressive cells. GBM patient sera were interrogated for the presence of anti-sperm/testicular antibodies, along with age-matched controls, utilizing monkey testicle sections. GBM patient serum contained anti-sperm/testicular antibodies at levels > six-fold that of controls. Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are associated with estrogenic tumors which appear to mimic placental tissue. We demonstrate that RORC-Tregs drive poor patient outcome, and Treg infiltration correlates strongly with androgen levels. Androgens support GBM expression of sperm/testicular proteins allowing Tregs from the patient's reproductive system to infiltrate the tumor. In contrast, estrogen appears responsible for MDSC/TAM immunosuppression.
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