Mechanisms of Cytokine-Induced Glioma Immunosuppression

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 naive T-cells. A separate cul- ture of T-cells (naive, 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 po- tentially through IL10 and IGFBP, and these cytokines also decrease IFN-� secretion from all varieties of T-cells suggest- ing 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.