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Original Research

Immunosuppressive activity of tumor-infiltrating myeloid cells in patients with meningioma

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Article: e1440931 | Received 04 Dec 2017, Accepted 10 Feb 2018, Published online: 15 Mar 2018
 

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.

Additional information

Funding

Italian Association for Cancer Research (AIRC) (IG2015-17400) Università degli Studi di Padova (CPDA-144873).

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