Patients with glioblastoma (GBM) exhibit profound systemic immune defects that affect the success of traditional and immune-based treatments. A better understanding of the contribution of the tumor and therapy on systemic and local immune suppression is necessary to improve immune based therapies and monitor the effects of conventional and novel therapies. To identify possible sources of immunosuppression, we measured the constituents of circulating immunity in newly diagnosed and recurrent GBM patients with or without dexamethasone treatment. We identified dexamethasone dependent and independent changes in systemic immunity associated with GBM. Of note, we identified a profound lymphopenia associated with dexamethasone treatement that manifested itself in the T cell compartment with targeted effects on the CD4+ T cells. In addition, we identified tumor and dexamethasone dependent altered monocyte phenotypes. The major population of altered monocytes (CD14+HLA-DRlo/neg) inhibited T cell proliferation, was unable to fully differentiate into mature dendritic cells, was associated with dexamethasone-mediated changes in CCL2 levels, and could be re-created in vitro using tumor supernatants. Interestingly, CD14+HLA-DRlo/neg monocytes were elevated similarly in newly diagnosed and recurrent patients. These data demonstrate that both tumor and steroids contribute to systemic immunosuppression. We provide evidence that tumors express high levels of the monocyte recruitment chemokine CCL2, can contain high numbers of CD14+ cells, that tumor supernatants can transform CD14+HLA-DR+ cells into CD14+HLA-DRlo/neg immune suppressors, and that dexamethasone reduces CCL2 in vitro and is correlated with reduction of CCL2 in vivo. Consequently, we have developed a model for tumor mediated systemic immune suppression via recruitment and transformation of CD14+ cells.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5303.