Fig. 2

The primary tumor promotes activation of CAFs through multiple modalities, including exosomes, cytokines, chemokines, and receptor activation. Activated CAFs achieve crosstalk with tumor metabolism through metabolic reprogramming, which stimulates the release of metabolites and inflammatory mediators and regulates the expression of related proteins, ultimately leading to tumor chemoresistance, ECM remodeling, metastasis, and the generation of an immunosuppressive TME