TNF and cancer: CAFs can be activated within the cancer microenvironment by physical changes to ECM (stiffness and composition), cell-to-cell contact signals (such as Notch), DNA damage (chemotherapy or radiotherapy), physiological stress (i.e., disrupted metabolism), inflammatory signals (e.g., transforming growth factor-β [TGFβ], interleukins 1 and 6 [IL-1, IL-6], tumor necrosis factor [TNF]) and growth factors (e.g., platelet derived growth factor [PDGF] and fibroblast growth factor [FGF]) (Sahai et al., 2020).