gms | German Medical Science

Objective: Current standard therapy of glioblastoma (GBM) patients offers dismal prognosis. The role of immunotherapy in the treatment of malignant gliomas is still a matter of research and requires detailed immune monitoring. This can be accomplished by flow cytometry as well as by functional assays.

Method: Using flow-cytometry and a panel of 50 antibodies the immunological characteristics of GBM patients were tested in whole blood samples before surgery. A validated chemiluminescence based ELISA (Siemens Immulite^®) was applied to identify a tumor-specific biomarker profile. Seven biomarkers were tested directed against differentiation antigens, we identified immune characteristics associated with immunosuppressive function against malignancies. (CD3+, CD4+, CD33+, CD39+, CD56+, HLA-DR+). Additionally IL-6, IL-8, IL-10, ferritin and IL-1beta levels were determined in plasma samples.

Results: In 31 patients, flow cytometry revealed several profiles indicative for immune suppression. One was the increased presence of CD4/CD25 (7/31) and CD39 positive regulatory T cells (6/31), a second profile was associated with impaired HLA-DR expression on circulating monocytes (6/31), a third profile was represented by increased numbers of neutrophil derived myeloid suppressor cells (nMDSCs) (16/31) and a fourth profile was identified by increased expression of CD33 (Siglec3) on monocytes (6/31), possibly representing mMDSCs. IL-10 and increased amounts of Ferritin were found in 26 % and 52 % of all patients investigated. We found a remarkable down-regulation of CD3+ and CD4+ T-cells in blood samples. Moreover, Tregs seem to infiltrate tumor tissue and promote immunosuppressive environment as well as increased levels of IL 10 and ferritin.

Conclusions: Several biomarkers can be identified in GBM patients using peripheral blood samples which may be crucial to follow during treatment and during remission. In addition, these markers may be valid to design a specific immune therapy using either vaccination and or dendritic cell therapy with and without additional immune modulators. Such approaches will improve the therapeutic response in patients with GBM. Immunological monitoring and modulation of the tumor environment is a first step to adequate and individualised therapy of GBM.