Identification of myeloid-derived suppressor cells that have an immunosuppressive function in NF2 patients
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.
We analyzed the expression of cytokines in the serum of NF2 patients and determined the percentage of HLA-DR−CD33+CD11b+ cells in blood and NF2-associated schwannomas. Furthermore, we analyzed the role of HLA-DR−CD33+CD11b+ cells in inhibiting T-cell proliferation, cytokine production, and transforming growth factor expression.
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-DR−CD33+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-DR−CD33+CD11b+ phenotype, and surgical removal of the tumor reduced the percentage of these cells.
HLA-DR−CD33+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.
KeywordsNF2 MDSCs Immunosuppression TGF-β
Neurofibromatosis type 2
Myeloid-derived suppressor cells
Transforming growth factor-β
Inducible nitric oxide synthase
Non-phagocytic cell oxidase 2
Peripheral blood mononuclear cell
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.
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 was obtained from all individual participants included in the study.
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