Malignant gliomas are tumors with a very unfavorable prognosis. They are
characterized by rapid proliferation and invasion in the surrounding healthy tissue. Complete
resection of the tumor is still the most important therapeutic option. Despite a variety of therapy
modifications in the last years, long term survivors are still rare. Dendritic cell vaccination
(DCV) might offer a new therapy option for the treatment of malignant gliomas. Hereby, tumorlysate
pulsed dendritic cells (TPDC) can prime T cells to generate anti-tumor immune responses.
Lenalidomide is an immune-modulatory piperidine-dione that has demonstrated activity
especially in the treatment of hematopoietic malignancies. Here, we tested the combination of
DCV and lenalidomide in an in vitro model for immunotherapy of malignant gliomas. No
changes of T or NK cell subsets were observed when lenalidomide was used. In addition,
interferon gamma enzyme linked immunospot (ELISPOT) showed no effects after priming of
autologous peripheral blood mononuclear cells (PBMC) with TPDC and challenge with tumor
cells. Although analyses of supernatants did not show higher amounts of interferon gamma and
tumor necrosis factor alpha in the presence of lenalidomide, enhanced immune reaction by lenalidomide was
detectable by granzyme B ELISPOT. Significantly higher numbers of spots were detected after challenge of TPDCprimed
PBMC with tumor cells in the case that lenalidomide was present in the culture medium during priming. Our
data suggest that the combination of DCV with lenalidomide might improve immunotherapy for malignant gliomas.
Keywords: Glioblastoma, immunotherapy, dendritic cell vaccination, immune modulation, lenalidomide, in vitro models.
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