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

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-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.

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-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.

CONCLUSIONS: 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.