The Open Cancer Immunology Journal

2010, 3 : 30-35
Published online 2010 December 31. DOI: 10.2174/1876401001003010030
Publisher ID: TOCIJ-3-30

Mechanisms of Cytokine-Induced Glioma Immunosuppression

Alexander Ksendzovsky , Roberta P. Glick , Paul Polak , Maria-Vittoria Simonini , Anothony J. Sharp , Tyler Newman , Edward P. Cohen and Douglas L. Feinstein
Chicago Medical School, North Chicago, IL, USA

ABSTRACT

Glioma immunosuppression includes the secretion of cytokines that down-regulate the host immune response resulting in tumor survival. The mechanisms of cytokine-induced immunosuppression are not well understood and are considered in this study. Glioma cells were incubated with supernatant from activated and naïve T-cells. A separate culture of T-cells (naïve, CD3-activated, and CD3/CD28 activated) was then incubated with conditioned media from the treated glioma cells as well as individual and combination recombinant cytokines. These T-cells were tested for viability, proliferation and IFN-􀀁 release. Several conclusions were drawn from these experiments: cytotoxicity is not a means of glioma immunosuppression, glioma conditioned media decreases proliferation of CD3/CD28 activated T-cells acting potentially through IL10 and IGFBP, and these cytokines also decrease IFN-􀀁 secretion from all varieties of T-cells suggesting that T-cell differentiation away from TH1 is another potential means of immunosuppression. These results necessitate further analysis of proliferation and differentiation as potential mechanisms of immunosuppression and the incorporation of this knowledge into the production of a more efficacious tumor vaccine.

Keywords:

Glioma, immunotherapy, cytokine, TGF-beta, immunosuppression.