Figure 1.

Overview of the tumor microenvironment (TME). Three ecosystems contribute to the TME: firstly, the cellular ecosystem that is composed of immune cells (lymphoid and myeloid), fibroblasts, mesenchymal stem cells (MSCs), pericytes, endothelial cells, and tumor cells. Secondly, the cell-to-cell membrane interactions and soluble secreted factors that participate in the intricate interplay among these cells, e.g., cytokines, chemokines, growth factors, hormones, proteolytic enzymes, and metabolites. Thirdly, the extracellular matrix (ECM) bed on which the cellular ecosystem resides, also providing biological signals to the tumor and stromal cells through ECM-derived peptides and the structural domains of its proteins. The interplay of these signaling networks and ecosystems promotes tumor cell proliferation, survival, epithelial-to-mesenchymal transition, drug resistance and loco-regional modulation, such that the TME is conducive to tumor cell invasion and metastatic spreading, angiogenesis and immune cell evasion.