Figure 1.

 Barriers to effective adaptive antitumor immune response. Tumors have developed multiple mechanisms to effectively inhibit the antitumor immune response. Starting with tumor immune recognition, lack of appropriate maturation signals leads to generation of tolerogenic DC’s, which prevents effective antigen presentation and generation of tumor-reactive T cells. Inhibition of production of appropriate attractive chemokines fails to recruit T cells to the tumor site. Tumor vasculature establishes a further barrier to tumor-reactive T cells. Tumor effects on vascular endothelial cells lead to downregulation of the adhesion molecules necessary for T-cell arrest and transmigration, as well as to expression of immunosuppressive ligands that act to inhibit T-cell function or even to kill T cells. The T cells that manage to transmigrate into the tumor stroma further encounter additional inhibitory barriers, which include suppression by MDSCs and Tregs through different mechanisms, leading to upregulation of inhibitory receptors, apoptosis, anergy, or exhaustion. Finally, the encounter with tumor cells may not lead to efficient lysis due to downregulation of MHC or specific TAAs on tumor cells, and increased expression of immunosuppressive proteins by the tumor cells that act to inhibit T-cell function. DC, dendritic cell; MDSC, myeloid-derived suppressor cell; MHC, major histocompatibility complex; TAA, tumor-associated antigen.