Fig. 1

Schematic diagram of TME components. TME consists of cell component, the extracellular matrix (ECM) and abundant soluble signaling molecules. ECM is a macromolecular substance secreted by cells into the extracellular space and constitutes a complex network that supports tissue structure and the physiological activities of cells, including collagen, elastin fibrils, proteinases, proteoglycans (PGs), glycoproteins and glycosaminoglycans (GAGs). Signaling molecules in the TME include cytokines (e.g. TGF-β), growth factors (e.g. VEGF) and degradation and remodeling enzymes (e.g. MMPs). Substantial cells are divided into immune cells and non-immune cells. Non-immune cells are composed of epithelial, smooth muscle, vascular, glial, fat cells and fibroblasts. The infiltrating immune cells in the TME constitute the main body of TIME. TIME possesses distinct populations of myeloid cells and lymphocytes, two major categories of immune systems that act synergistically to initiate and reinforce innate and adaptive immunity in human, including macrophages, neutrophils, myeloid-derived suppressor cell (MDSC), B cells, T cells, natural killer (NK) cells, dendritic cells (DCs)