Mechanisms of Cytokine-Induced Glioma Immunosuppression



Alexander Ksendzovsky*, 1, Roberta P. Glick2, Paul Polak3, Maria-Vittoria Simonini3, Anothony J. Sharp3, Tyler Newman3, Edward P. Cohen4, Douglas L. Feinstein3
1 Chicago Medical School, North Chicago, IL, USA
2 Mt. Sinai Hospital Dept. Neurosurgery, Rush College of Medicine Dept. Neurosurgery, University of Illinois - Chicago Dept. Anatomy and Cell Biology, Chicago, IL, USA
3 University of Illinois – Chicago Dept. Anesthesia, Jesse Brown Veterans Affair Hospital, Chicago, IL, USA
4 UIC Dept. Microbiology and Immunology, Chicago, IL, USA


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© 2010 Ksendzovsky et al.;

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Chicago Medical School, North Chicago, IL, USA; Tel: (404)550-5694; Fax: (312) 996-9680; E-mail: aksendz@my.rfums.org


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.