Fig. 7.

Proposed model of GBM induced immunosuppression by CD14⁺HLA-DR^lo/neg monocytes. In GBM, tumor derived factors like CCL2 recruit CD14⁺ cells to the tumor environment whereby they are exposed to tumor derived factors and other immunosuppressive cytokines. Subsequently, CD14⁺HLA-DR⁺ monocytes become CD14⁺HLA-DR^lo/neg monocytes. DEX down-regulates specific cytokine expression within the tumor (like CCL2), thus inhibiting the recruitment of monocytes to the tumor or releasing of CD14⁺HLA-DR^lo/neg monocytes from the tumor microenvironment into the bloodstream (upper panel). Under normal conditions, CD14⁺HLA-DR⁺ monocytes differentiate into mature DCs and activate responder T cells. CD14⁺HLA-DR^lo/neg monocytes are unable to fully differentiate into mature DCs and also directly inhibit T cell responses.