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Identification of myeloid-derived suppressor cells that have an immunosuppressive function in NF2 patients

  • Ying Wang
  • Peng Li
  • Bo Wang
  • Shuai Wang
  • Pinan LiuEmail author
Original Article – Clinical Oncology

Abstract

Purpose

There is no targeted drug therapy for NF2 patients, and surgery or radiosurgery is not always effective. Therefore, the exploration of new therapeutic pathways is urgently needed.

Methods

We analyzed the expression of cytokines in the serum of NF2 patients and determined the percentage of HLA-DRCD33+CD11b+ cells in blood and NF2-associated schwannomas. Furthermore, we analyzed the role of HLA-DRCD33+CD11b+ cells in inhibiting T-cell proliferation, cytokine production, and transforming growth factor expression.

Results

NF2 patients are in an immunosuppressed state with elevated IL-10 and TGF-β expression in plasma and the lymphocytes from NF2 patients secrete less IFN-γ and CD3+ T cells proliferate slower than normal healthy donors. HLA-DRCD33+CD11b+ cells frequency significantly increased in the PBMCs and infiltrated in the tumor, these cells express higher iNOS, NOX2 and TGF-β, and induce TGF-β secretion to inhibit CD8+ T-cell proliferation, and induce T-cell transformation to a CD4+CD25+Foxp3+ regulatory T cells phenotype. NF2-associated schwannoma cells induced monocytes transformation into an HLA-DRCD33+CD11b+ phenotype, and surgical removal of the tumor reduced the percentage of these cells.

Conclusions

HLA-DRCD33+CD11b+ cells may represent a population of MDSCs in NF2 patients. Dissecting the mechanisms behind these suppressive mechanisms will be helpful for the design of effective immunotherapeutic protocols and likely provide a new effective treatment for NF2 patients.

Keywords

NF2 MDSCs Immunosuppression TGF-β 

Abbreviations

NF2

Neurofibromatosis type 2

MDSC

Myeloid-derived suppressor cells

TGF-β

Transforming growth factor-β

iNOS

Inducible nitric oxide synthase

NOX2

Non-phagocytic cell oxidase 2

ARG-1

Arginase-1

PBMC

Peripheral blood mononuclear cell

TCR

T-cell receptor

Notes

Funding

This work was supported by grants from National Natural Science Foundation of China (No. 81502453) and Natural Science Foundation of Beijing Municipality (No. 7162057).

Compliance with ethical standards

Conflict of interest

The authors declare no potential conflicts of interest.

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.

Supplementary material

432_2018_2825_MOESM1_ESM.docx (7.2 mb)
Supplementary material 1 (DOCX 7350 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina
  2. 2.Department of Neurosurgery, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina

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