Transforming growth factor beta 1 (TGFB1) (TGFB1)

Transforming growth factor beta 1 (TGF-β1) is a pleiotropic cytokine that serves as a master regulator of immune homeostasis, tissue repair, and cell growth (UniProt P01137). In oncology, TGF-β1 is traditionally recognized as a potent immunosuppressive factor within the tumor microenvironment, where it inhibits the effector functions of Natural Killer (NK) cells and T cells to facilitate tumor evasion (PubMed: 30249712). However, recent research into "ultra-low dose" (UD) TGF-β imprinting has revealed a paradoxical role: minimal concentrations of the cytokine can prime NK cells for enhanced anti-tumor activity. These UD-TGFβ-imprinted NK cells exhibit significantly increased expression of innate activating receptors, such as NKG2D and NKp44, as well as death ligands like TRAIL and FasL, which mediate the direct recognition and killing of tumor cells (Foltz et al., 2018). Therapeutic approaches targeting the TGF-β pathway include neutralizing monoclonal antibodies like fresolimumab, small molecule inhibitors of the TGF-β receptor kinases like galunisertib, and bifunctional fusion proteins like bintrafusp alfa. While these therapies aim to restore anti-tumor immunity, their clinical development is complicated by the cytokine's complex biology, leading to potential safety concerns such as cardiotoxicity and the development of squamous skin lesions (StatPearls: NBK538140).

Other names

TGF-beta 1Transforming growth factor beta-1TGFBCEDLAPLatency-associated peptideDPD1

Inhibition of TGF-beta signaling through ligand neutralization, receptor kinase inhibition, or ligand sequestration (trapping).