http://orcid.org/0000-0002-8927-2410 http://orcid.org/0000-0002-8927-2410 http://orcid.org/0000-0002-8927-2410
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ABSTRACT
Meningiomas WHO grade I and II are common intracranial tumors in adults that normally display a benign outcome, but are characterized by a great clinical heterogeneity and frequent recurrence of the disease. Although the presence of an immune cell infiltrate has been documented in these tumors, a clear phenotypical and functional characterization of the immune web is missing. Here, we performed an extensive immunophenotyping of peripheral blood and fresh tumor tissue at surgery by multiparametric flow cytometry in 34 meningioma patients, along with immunosuppressive activity of sorted cells of myeloid origin. Four subsets of myeloid cells, phenotypically corresponding to myeloid-derived suppressor cells (MDSCs) are detectable in the blood and in the tumor tissue of patients and three of them are significantly expanded in the blood of patients, but show no evidence of suppressive activity. At the tumor site, a large leukocyte infiltrate is present, predominantly constituted by CD33+ myeloid cells, largely composed of macrophages endowed with suppressive activity and significantly expanded in grade II meningioma patients as compared to grade I.
Abbreviations
| ARG-1 | = | Arginase-1 |
| eMDSC | = | early MDSC |
| FACS | = | fluorescence- activated cell sorting |
| FMO | = | fluorescence minus one |
| FSC | = | forward scatter |
| HD | = | healthy donors |
| IL4Rα | = | α chain of interleukin 4 receptor |
| LAG-3 | = | lymphocyte-activation gene 3 |
| Lin | = | lineage cocktail |
| MDSC | = | myeloid-derived suppressor cell |
| MDSC-LC | = | MDSC-like cells |
| MDSC 1 | = | CD14+/IL4Rα+ cells |
| MDSC 2 | = | CD15+/IL4Rα+ cells |
| MDSC 3 | = | Lin−/HLA-DR−/CD11b+/CD33+ cells |
| MDSC 4 | = | CD14+/HLA-DRlow/− cells |
| MG | = | meningioma |
| MGG | = | May-Grünwald Giemsa |
| M-MDSC | = | monocytic MDSC |
| n | = | number |
| NA | = | not applicable |
| PBMC | = | peripheral blood mononuclear cell |
| PBL | = | peripheral blood leukocytes |
| PD-1 | = | programmed death 1 |
| PD-L1 | = | Programmed death-ligand 1 |
| PMN | = | polimorphonuclear cell |
| PMN-MDSC | = | polymorphonuclear MDSC |
| SD | = | standard deviation |
| SE | = | standard error |
| SSC | = | side scatter |
| TAM | = | tumor-associated macrophage |
| TIM-3 | = | T cell immunoglobulin and mucin protein 3 |
| WHO | = | World Health Organization |
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.