Fig. 2

Tumor immunosuppressive microenvironment. The TME plays an important role in immune tolerance. The aspects of the complex TME that can sustain tumor growth, promote immune escape, and enhance immunosuppressive features are hypoxia, hypoglucosis, lactosis, acidity, and nutrient deprivation. Furthermore, changes in signal transduction molecules, the loss of tumor-specific antigens, stimulation of the inhibiting receptor CTLA-4 on T-cells, and some soluble molecules (IL-10, IL-35, type I IFNs, IDO, adenosine, VEGF-A, and TGF-) secreted by tumor cells or non-tumor cells in the TME all contribute to immune cell dysfunction. Moreover, the TME contains immunosuppressive cells (Tregs, MDSCs, TAMs, and CAFs) which contribute to immune cell dysfunction. Abbreviations: TME (tumor microenvironment), TSAs (tumor-specific antigens), CTLA-4 (cytotoxic T-lymphocyteassociated antigen 4), IFNs (interferons), IDO (Indoleamine 2,3-Dioxygenase), VEGF-A (vascular endothelial growth factor A), TGF-β, transforming growth factor-beta, Tregs (Regulatory T-cells), MDSCs (myeloid-derived suppressor cells), TAMs (tumor-associated macrophages), CAFs (cancer-associated fibroblasts)