Lenalidomide in an in vitro Dendritic Cell Model for Malignant Gliomas

Abstract

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.

Antitumor effect of lenalidomide in malignant glioma cell lines

“…The present study was designed to investigate the direct antitumor effect of lenalidomide on malignant glioma cell lines including cell cycle arrest and apoptosis induction. The findings of previous studies indicated that lenalidomide exerted an antitumor effect on gliomas especially enhancement of immune reactions such as interferon secretion from T cells (26,27).…”

“…Lenalidomide exerts an antitumor effect due to enhancement of the cytotoxic effect in T cell interferon-γ secretion. Kuhnol et al reported that the immune reaction was enhanced by lenalidomide in in vitro models (27). These studies evaluated the antitumor effect of immune cells induced by lenalidomide.…”