Impact of Androgen Signaling on the Composition of the Immune Microenvironment in Glioblastomas (Andro-iGlio)

Glioblastoma (GBM) is the most common and most aggressive primary brain cancer in adults. GBM is more common in men than in women, with a male-to-female ratio of 1.6. Furthermore, being male is associated with a poorer prognosis. These data suggest that sex and/or sexual hormones and more specifically androgens may play a role in the initiation, the growth, and the resistance to treatments of GBM.

Study Overview

• Status: Not yet recruiting
• Conditions: Glioblastoma (GBM)
• Intervention / Treatment: Other: blood sampling; Other: saliva sampling; Other: stool sampling; Other: Tumor sampling

Detailed Description

Glioblastoma (GBM) is the most common and most aggressive primary brain tumor in adults, with an annual incidence in France of approximately 2,500-3,500 new cases. Despite intensive multimodal treatment, the median overall survival remains less than 18 months.

For reasons that are not yet fully understood, GBM occurs more frequently in men than in women, with a male-to-female ratio of approximately 1.6. Moreover, male sex appears to be associated with a poorer prognosis, as men diagnosed with GBM tend to have shorter survival compared with women. Importantly, such sex-based differences are not restricted to GBM; with few exceptions, they are also observed in most non-hormone-dependent systemic cancers.

These epidemiological and clinical observations suggest that sex and/or sex steroid hormones-particularly androgens-may contribute to GBM biology. The effects of androgens are primarily mediated through their binding to the androgen receptor (AR). Preliminary data indicate that AR is expressed not only by GBM tumor cells but also by cells within the tumor microenvironment, especially cells of the myeloid lineage, including microglia and tumor-associated macrophages.

In addition, some studies have shown that certain GBM cells are capable of producing dihydrotestosterone. Taken together, these findings support a potential role for androgen signaling in modulating both tumor cells and the immune microenvironment in GBM. They also provide a rationale for evaluating anti-androgen therapies, either alone or in combination with other treatment modalities, including immunotherapies, in patients with GBM.

Further support for this hypothesis comes from studies in systemic cancers. In prostate cancer, for example, anti-androgen therapy has been shown to increase cytotoxic T lymphocyte infiltration. Combinations of hormone therapy and immunotherapy have been tested in preclinical models, demonstrating reduced androgen-induced immunosuppression and enhanced sensitivity to immune checkpoint inhibitors, an approach currently being explored in clinical trials. Moreover, in melanoma-a non-hormone-dependent cancer such as GBM-AR silencing increases cytotoxic T-cell infiltration, reduces regulatory T-cell infiltration, and decreases the expression of immune inhibitory molecules such as LAG-3 and PD-1.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ahmed IDBAIH, MD-PhD; Phone Number: +33 01 42 16 03 85; Email: ahmed.idbaih@aphp.fr
• Study Contact Backup: Name: Maïté VERREAULT, PhD; Phone Number: +33 01 57 27 43 91; Email: maite.verreault@icm-institute.org

Study Locations

• France
  • Paris, France, 75013
    • Neuro-oncology department, Pitié Salpêtrière hospital
    • Contact: Ahmed IDBAIH, MD-PhD; Phone Number: +33 01 42 16 03 85; Email: ahmed.idbaih@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients aged ≥18 and ≤55
• Newly diagnosed GBM
• Surgery with complete or incomplete resection
• Eligible for chemoradiotherapy
• No active immune disorders
• Supratentorial location on MRI and no signs of meningeal dissemination
• Tumor sample (taken as part of treatment) available for study (fresh frozen tissue)
• Patient informed and consented to participate in the study
• Affiliation with a social security system or beneficiary

Exclusion Criteria:

• Active infection at the time of sampling or within the previous 14 days
• Active immune disorders
• Known patients with low-grade glioma that has undergone anaplastic transformation
• Patients treated with corticosteroids
• Patients participating in interventional research
• Patients under legal protection, guardianship, or conservatorship.
• Pregnant or breastfeeding women
• Individuals under AME

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Glioblastoma patients; Adult men and women with GBM who are being treated in the neuro-oncology department at La Pitié-Salpêtrière Hospital.

Other: blood sampling; Additional blood samples (in addition to those taken as part of treatment) will be taken from patients at T1 (before any medical treatment) and at T2 (one month after the end of concomitant chemoradiotherapy). These samples, totaling 6 to 8 mL, will be taken between 9 a.m. and 11 a.m. (this time slot allows patients to normalize their circadian rhythm); Other: saliva sampling; During these same visits at T1 and T2, a saliva sample will be collected using Salivette® Cortisol saliva collection devices (UGAP ref.: 2745674); Other: stool sampling; During these same visits at T1 and T2, a stool sample will be collected by the patient using the kit (Stool Sample Collection Kit with Stool Catcher, Canvax); Other: Tumor sampling; At the time of surgery performed as part of treatment (before T1), tumor tissue from the surgical waste will be collected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean expression of AR, ER, and other hormone signaling pathway genes in the tumor	Expression of AR, ER, and other hormone signaling pathway genes using tumor RNA sequencing data	Baseline: Before any treatment; 4 to 6 weeks after completion of the concurrent radiochemotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean of Percentage of immunosuppressive cells measured at T1 and T2 in the blood and tumor	Percentage of immunosuppressive cells measured at T1 and T2 in the blood and tumor using spectral cytometry	Baseline: Before any treatment; 4 to 6 weeks after completion of the concurrent radiochemotherapy
Profile of immunosuppressive cytokines in the tumor	Profile of immunosuppressive cytokines in the tumor (quantification of a panel of cytokines)	Baseline: Before any treatment; 4 to 6 weeks after completion of the concurrent radiochemotherapy
Mean of the Proportion of intratumoral immune cells	Proportion of intratumoral immune cells via the deconvolution of tumor RNA sequencing data	Baseline: Before any treatment; 4 to 6 weeks after completion of the concurrent radiochemotherapy

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Ahmed IDBAIH, MD-PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2030

Study Registration Dates

• First Submitted: February 16, 2026
• First Submitted That Met QC Criteria: March 10, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Glioblastoma; Androgen
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: APHP241106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.

Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.

• IPD Sharing Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No