Second, Tregs promote physical barrier formation by triggering matrix remodeling and abnormal tumor vasculogenesis through multiple mechanisms: Treg-secreted TGF-β induces CAF differentiation, driving collagen crosslinking and fibrin deposition to form dense ECM that hinders neoantigen-specific TIL migration (65); Tregs also secrete VEGF-A and IL-10 to promote immature, leaky vasculature, which impedes effector cell infiltration (66). This evidence concerns the gene TGFB1 and neoplasm.