Aberrant cytokine/chemokine signalling in KRAS-mutant tumours, such as IL-1β, IL-8, TGF-β and CXCL1 [34, 98], can also result in structural remodelling of the TME extracellular matrix (ECM) by neutrophils, CAFs [99] and M1 macrophages [34] resulting in degradation of ECM by MMP-9 and collagenase IV and the release of bound angiogenic factors such as VEGF [99], as well as cross-linking of ECM collagen fibres by lysyl oxidases (LOX) to enhance matrix stiffness and provide a physical barrier for immune cell infiltration (Fig. 2) [99, 100]. This evidence concerns the gene TGFB1 and neoplasm.