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-DRCD33CD11b cells in blood and NF2-associated schwannomas. Furthermore, we analyzed the role of HLA-DRCD33CD11b 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-DRCD33CD11b 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 CD4CD25Foxp3 regulatory T cells phenotype. NF2-associated schwannoma cells induced monocytes transformation into an HLA-DRCD33CD11b phenotype, and surgical removal of the tumor reduced the percentage of these cells.

CONCLUSIONS

HLA-DRCD33CD11b 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.