Is an Immunosuppressive Microenvironment a Characteristic of Both Intra- and Extraparenchymal Central Nervous Tumors?

Abstract

In spite of intensive research, the survival rates of patients diagnosed with tumors of the central nervous system (CNS) have not improved significantly in the last decade. Immunotherapy as novel and efficacious treatment option in several other malignancies has failed in neuro-oncology likely due to the immunosuppressive property of the brain tissues. Glioblastoma (GBM) is the most aggressive malignant CNS neoplasm, while meningioma (MNG) is a mainly low grade or benign brain tumor originating from the non-glial tissues of the CNS. The aim of the current preliminary study is to compare the immune microenvironment of MNG and GBM as potential target in immunotherapy. Interestingly, the immune microenvironment of MNG and GBM have proved to be similar. In both tumors types the immune suppressive elements including regulatory T cells (Treg), tumor-associated macrophages (TAM) were highly elevated. The cytokine environment supporting Treg differentiation and the presence of indoleamine 2,3-dioxygenase 1 (IDO1) have also increased the immunosuppressive microenvironment. The results of the present study show an immune suppressive microenvironment in both brain tumor types. In a follow-up study with a larger patient cohort can provide detailed background information on the immune status of individual patients and aid selection of the best immune checkpoint inhibitor or other immune modulatory therapy. Immune modulatory treatments in combination with IDO1 inhibitors might even become alternative therapy for relapsed, multiple and/or malignant MNG or chemo-resistant GBM.

Novel Human Meningioma Organoids Recapitulate the Aggressiveness of the Initiating Cell Subpopulations Identified by ScRNA‐Seq

“…These results suggested that the SULT1E1 + subpopulation in high‐grade meningiomas may directly contribute to the formation of an immunosuppressive environment, which is a common characteristic of aggressive tumors. [ 30 ] Targeting the CSF1‐CSF1R axis has been suggested as a potential treatment strategy for malignant meningiomas, [ 24b ] and combination therapies targeting both CSF1‐CSF1R axis and SULT1E1 + subpopulation may be a more effective immunotherapy for high‐grade meningiomas.…”

A Review of the Role of Stereotactic Radiosurgery and Immunotherapy in the Management of Primary Central Nervous System Tumors

“…In a 1994 study by Klein et al, where escalating radiation doses were delivered to glioblastoma specimens, exposure to RT was linked to an increase in major histocompatibility complex class I antigen expression, suggesting an increase in cytotoxic T-cell activity against glioblastoma [ 96 ]. Additionally, a recent study by Soltani et al suggested that glioblastomas and low grade meningiomas share similarities in their tumor microenvironments which are associated with immunosuppression [ 97 ].…”