Role of the Tumor Microenvironment in Aggressive Meningiomas

Study Purpose

Meningiomas are the most common primary tumors of the central nervous system in adults. High-grade forms have a high frequency of neurofibromatosis 2 (NF2) mutations and represent 25% of meningiomas, with multiple recurrences associated with morbidity and reduced survival without medical options, including immunotherapy. The meninges play a key role in neuro-immune communication through the diversity of their immune cells and the presence of meningeal lymphatic vessels (MLV). Recent data, including from our team, shows frequent infiltration of lymphocytes and myeloid cells specific to benign meningiomas. Our hypothesis is that the immune microenvironment composed of meningeal immune cells and MLVs regulates the malignant histological progression of NF2-mutated meningiomas and their immune surveillance evasion behavior This study aims to characterize the different cellular populations of the meningioma microenvironment. We will describe the exact participation of immune and vascular cell populations in the initiation and progression of meningioma, using MRI imaging and surgical biopsies of the dura mater and meningioma in patients undergoing neurosurgery for meningioma resection.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Patients who underwent surgery for the resection of a meningioma. 2. Patients with meningiomas located at the convexity and parasagittal regions. 3. Patients aged 18 years or older. 4. Patients who were informed of the study and did not express opposition to their participation.

Exclusion Criteria:

- Individuals under legal protection (guardianship, trusteeship) safeguarded by justice

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05821790
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Assistance Publique - Hôpitaux de Paris
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Michel KALAMARIDES, MD
Principal Investigator Affiliation	APHP
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Meningioma

Additional Details

The objective of this study is to characterize the different cellular populations of the microenvironment of meningioma, particularly the immune and vascular cell populations, in order to better understand their role in the initiation and progression of this tumor. For this purpose, we will use MRI imaging and surgical biopsies of the dura mater and meningioma to characterize cellular phenotypes and their interactions in the tissue microenvironment. The research will be conducted on a cohort of patients treated for meningioma in neurosurgery services. Samples required for the study will be obtained from surgical waste of patients who underwent meningioma resection. Data necessary for the study will be collected from the patient's medical records, MRI examinations, and data specific to the characteristics of the surgical waste. Prospective patients will be informed of the study through an information note. Patients who do not object to their participation will undergo neurosurgery intervention in accordance with the usual service protocol. During the intervention, surgical waste will be produced, including the meningioma and adjacent dura mater, which will be collected under the responsibility of the neuro-pathologist who will also take fragments for routine diagnostic histological analysis. We will then perform a targeted mutational analysis associated with neuropathological evaluation of the tumor grade in order to select 10 cases of grade I meningioma and 10 cases of grade II and III meningioma carrying the NF2 mutation. An in-depth analysis will then be carried out on these samples using 10x Genomic's single-cell RNA sequencing (scRNA-seq) technology. This analysis will help to understand the tumor's heterogeneity and establish the phenotype and differentiation trajectory of tumor cells, dura mater cells, and associated immune cells. In addition to RNA analysis, the expression of genetic signatures will be validated by RNAscope tests, while Hyperion imaging will allow visualization of the interrelationships between different types of cells and their spatial distribution. The iDISCO+ immunolabeling combined with three-dimensional fluorescence microscopy imaging will enable visualization of specific protein expression profiles of meningioma and dura mater cell types in 3D. Once the analyses are complete, meningioma and dura mater samples will be destroyed. Preoperative MRI images will also be retrieved and analyzed.

Arms & Interventions

Arms

: patients treated for meningioma

Samples required for the study will be obtained from surgical waste of patients who underwent meningioma resection.

Interventions

Other: - Surgical waste and Data collect

Samples required for the study will be obtained from surgical waste of patients who underwent meningioma resection. Data necessary for the study will be collected from the patient's medical records, MRI examinations, and data specific to the characteristics of the surgical waste.