They can be activated by various stimuli in cancerous tissues, including TGF-β, inflammatory factors such as IL-1, IL-6, and TNF-α, physiological and genomic stress, ECM changes, and contact signals.304–306 In addition, CAFs promote tumor growth by remodeling the ECM, inducing immune evasion, and directly interacting with tumor cells.304 It has been confirmed that they emerge and contribute to the earliest stage of tumorigenesis (Table 3). This evidence concerns the gene IL6 and neoplasm.