Role of the Tumor Microenvironment in Aggressive Meningiomas (MEME)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Meningioma
• Intervention / Treatment: Other: Surgical waste and Data collect

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: Michel KALAMARIDES, MD; Phone Number: 33 1 42 16 31 12; Email: michel.kalamarides@aphp.fr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients who underwent surgery for the resection of a meningioma

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
patients treated for meningioma; Samples required for the study will be obtained from surgical waste of patients who underwent meningioma resection.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cellular phenotypes and their interactions in the tissue microenvironment	Characterized by combining different techniques and analysis systems (RNA-seq, RNAScope, Hyperion, Hyperion immunostaining) using samples from various grades of meningiomas and associated dura mater	one day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expressed genes in meningioma	Differential expression and gene ontology of expressed genes in meningioma cells, dura mater cells, and associated immune cells, obtained through scRNA-seq and RNAscope analyses using samples from various grades of meningiomas and dura mater	one day
cell types and spatial distribution	The cell types and their spatial distribution in meningiomas and associated dura mater characterized by the Hyperion cellular imaging system	One day
Visualization of interrelations in the spatial context	Using the Hyperion cellular imaging system	One day
3D protein expression	Specific 3D protein expression profiles of cell type in meningiomas and associated dura mater obtained through iDISCO+ immunolabeling combined with fluorescence microscopy imaging	One day
Three-dimensional reconstruction	Three-dimensional reconstruction of the lymphatic vessels and their cervical lymph nodes associated with pre-surgery MRI data.	One day

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Gustave Roussy, Cancer Campus, Grand Paris; Paris Brain Institute
• Investigators: Principal Investigator: Michel KALAMARIDES, MD, APHP

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): May 1, 2024
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: April 7, 2023
• First Submitted That Met QC Criteria: April 7, 2023
• First Posted (Actual): April 20, 2023

Study Record Updates

• Last Update Posted (Actual): April 20, 2023
• Last Update Submitted That Met QC Criteria: April 7, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: neurosurgery; immune cells; NF2; meningioma; meningeal lymphatic vessels; meningeal micro-environment
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Meningioma
• Other Study ID Numbers: APHP230289

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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