Fig. 12

Metabolic interactions in the TME. The TME is represented in the center by a group of cancer cells coated with activated fibroblasts and surrounded by CAFs and immune cells. At the top: In hypoxic condition, TME promotes the production of angiogenic factors (VEGF, TGF-β, FGF and PDGF) to induce rapid angiogenesis, resulting in the formation of aberrant blood vessels with reduced pericyte coverage, low levels of leukocyte adhesion molecules, and low levels of T-cell recruiting cytokines, therefore impeding the recruitment of anti-tumor immune cells. On the left: under certain stimuli, CAFs are activated and acquire a pro-inflammatory signature with the expression of immunomodulatory molecules (TGF-β and PDL-1) and lead to ECM remodeling into a rigid fibrotic matrix. They also form a stromal matrix surrounding the tumor core through the desmoplastic reaction. On the right: Cancer cells drain energy from the surrounding immune cells by competing for nutrients and amino acids, stealing their mitochondria through nanotubes, and hiding from them using protective stromal matrix formed by CAFs which limits cytotoxic cell infiltration. CAF: CAFs: Cancer-associated fibroblasts; VEGF: Vascular endothelial growth factor; TGF-β: Transforming growth factor-β; FGF: Fibroblast growth factor; PDGF: Platelet-derived growth factor; PDL-1: Programmed death-ligand 1. This figure has been created with BioRender.com