CMV-specific immune responses induced by dendritic cell vaccines in glioblastoma patients

Glioblastoma multiforme (GBM) is a WHO grade IV malignant glioma and is the most common primary brain tumor. It has one of the poorest prognoses of all cancers, with a median survival of <15 months despite standard therapy with maximal surgical resection followed by radiotherapy and temozolomide treatment. Therapies intended to boost the patient's immune system, such as vaccine-based immunotherapies, have shown promising results in prolonging progression free survival and overall survival in many cancers, including GBM. Six patients diagnosed with GBM who received dendritic cell (DC)-vaccinations against CMVpp65 protein, telomerase reverse transcriptase (hTERT) peptides, and survivin peptides were tested for immune responses before and after each vaccination to see if immune responses could be induced by the vaccines and if it had an impact on the survival. This was investigated by proliferation assays, ELISpot assays, and flow cytometry looking at T cell activation and function. Peripheral blood mononuclear cells (PBMCs) and tumor-infiltrating lymphocytes (TILs) were analyzed by mass cytometry to investigate local immune activity. All patients showed induced immune responses against at least one of the vaccine antigens in either proliferation assays or IFN-γ ELISpot assays. The strongest responses in the patients were against the CMVpp65 protein, and one patient also showed increased IFN-γ production against hTERT peptide mix in the ELISpot assay. Intracellular staining followed by flow cytometry showed that the T cells produced TNF-α and/or IFN-γ in response to their cognate antigen, and there was a mix of cytokine producing CD8+ and CD4+ T cells, depending on the patient and antigen. Mass cytometry of PBMCs and TILs, where available, also showed expression of different markers indicative of activation and/or previous exposure to antigens. Although there were too few patients included in this study to conclude, the results suggest that immune responses were induced by DC vaccines. One of the patients had an ...