transforming growth factor-beta

Overview

Transforming growth factor-beta (TGF-β) is a multifunctional cytokine family with broad roles in cell growth, differentiation, extracellular matrix production, immune regulation, and tissue repair. In biomedical research, TGF-β is especially important because it can act as a context-dependent regulator: in some settings it supports normal homeostasis and wound healing, while in others it contributes to fibrosis, immune suppression, epithelial-to-mesenchymal transition, and tumor progression. Its signaling is commonly discussed together with the Smad pathway, as well as non-canonical routes such as MAPK signaling.

In disease biology, TGF-β is frequently implicated in fibrotic disorders, chronic kidney disease, pulmonary arterial hypertension, tracheal scarring, myocardial fibrosis, and tumor microenvironment remodeling. It also intersects with immune cell differentiation and function, including regulatory T cells, natural killer cells, B cells, macrophages, and neutrophil biology. Because of this dual biology, TGF-β is both a mechanistic biomarker and a therapeutic target in oncology, fibrosis, and immunomodulation.

Focus of Latest Publications

Recent publications have continued to position transforming growth factor-beta (TGF-β) as a central signaling node in cancer, fibrosis, and immune regulation. In intrahepatic cholangiocarcinoma, TGF-β signaling was linked to MyD88-driven glycolysis and malignant behavior: miR-7-5p suppressed TGF-β-induced glycolysis and proliferation by targeting MyD88, and TGF-β activation reversed the inhibitory effects of MyD88 knockdown. In Ewing sarcoma, TGF-β-mediated immunosuppression was addressed through TGF-β1-imprinted natural killer cells, designed to overcome tumor microenvironment resistance in combination with IL1RAP CAR targeting, an IL-15 agonist, and anti-GD2 antibody therapy. TGF-β also emerged in studies of immune evasion and resistance, including analyses of TGF-β-associated epithelial-to-mesenchymal transition signatures in single-cell drug-response profiling and reports that elevated TGF-β in recurrent head and neck squamous cell carcinoma can impair immune-cell penetration and reduce immunotherapy responses.

Several studies focused on TGF-β as a driver of fibrotic remodeling and epithelial-mesenchymal transition. Paeoniae Decoction was reported to attenuate chronic colitis-associated intestinal fibrosis by suppressing TGF-β/Smad-mediated epithelial-mesenchymal transition and remodeling the metabolic microenvironment. In liver fibrosis, cord-blood platelet-rich plasma reduced fibrogenic features of TGF-β-activated hepatic stellate cells, with downregulation of fibrosis-associated genes and proteins including COL1A1, MMP2, XBP1, GLI2, collagen, fibronectin, and TGF-β itself. In tracheal scar inhibition, a chitosan nanoparticle-incorporated polylactic acid/tacrolimus membrane suppressed hypertrophic scar fibroblast proliferation and collagen production by downregulating TGF-β and α-smooth muscle actin. In pancreatic ductal adenocarcinoma, targeted nanotheranostics mitigated radiation-induced fibrosis by deactivating pancreatic stellate cells induced by radiation and TGF-β, reducing α-SMA, collagen I, and fibronectin and improving immune infiltration. TGF-β was also implicated in thoracic aortic aneurysm growth arrest in aging Marfan mice, where modulation of TGF-β signaling was highlighted as a potential strategy to limit aneurysmal expansion.

In oncology immunotherapy, TGF-β was repeatedly studied as a barrier to antitumor activity and as a therapeutic target for combination approaches. In EGFR-mutant lung cancer, TGF-β inhibition potentiated osimertinib-induced antitumor immunity; osimertinib increased tumor TGF-β expression, and combination treatment with nintedanib or vactosertib increased effector T cells, increased Granzyme B-positive areas, decreased CD206-positive cells, and reduced TGF-β and SMAD2/3 expression. In recurrent cervical cancer, an anti-PD-L1/TGF-β bifunctional fusion protein was associated with distinct clinical outcomes and changes in immune-related gene expression, with TGF-β signaling pathways implicated in treatment response. Immune modulatory vaccine reviews also identified TGF-β as a tumor microenvironment antigen of interest for next-generation vaccines aimed at reprogramming suppressive stromal and myeloid compartments. In oral squamous cell carcinoma, TGF-β-mediated differentiation of ITGA1+ myofibroblastic cancer-associated fibroblasts contributed to CD8+ T cell exhaustion, and dual-targeted nanoparticles were used to disrupt this stromal-immune axis.

Beyond cancer and fibrosis, TGF-β was also linked to inflammatory and metabolic disease mechanisms. In atherosclerosis, TGF-β was described as a convergent signaling pathway driving endothelial-to-mesenchymal transition, alongside Wnt/β-catenin, Notch, NF-κB/STAT3, and epigenetic regulators. curcumin reduced foam cell formation in ox-LDL-treated macrophages and downregulated TGF-β together with P2X7R, NOX1, and MMP-3. In idiopathic pulmonary fibrosis, TGF-β was noted as a profibrotic mediator downstream of M2 macrophage polarization and ADORA2B signaling, and inhaled biomimetic nanoparticles reduced these upstream drivers and ameliorated fibrosis. In Duchenne muscular dystrophy, an engineered mitochondria-targeted peptide reduced inflammation by inhibiting IL-6 and TGF-β, while also suppressing fibrosis and promoting myogenesis. Collectively, these publications reinforce TGF-β as a broadly relevant target in tumor progression, immune suppression, and tissue fibrosis, with recent work emphasizing pathway inhibition, ligand imprinting, and combination nanomedicine strategies.

Key Publications

• NEWJul MiR-7-5p suppresses TGF-β-induced glycolysis and proliferation in intrahepatic cholangiocarcinoma by targeting MyD88. (Human cell, 2026, PMID 42400723): "Considering that TGF-β signaling and aerobic glycolysis provide a favorable growth environment for tumors, this study aims to explored the relationship between the miR-7-5p/MyD88 axis and these metabolic characteristics."
• NEWJul Circumventing Ewing sarcoma tumor microenvironment resistance by IL1RAP CAR-modified TGFβ1-imprinted natural killer cells in combination with IL-15 agonist and anti-GD2 antibody. (Journal for immunotherapy of cancer, 2026, PMID 42398968): "...circumventing transforming growth factor beta (TGFβ)-mediated NK immunosuppression by TGFβ1-imprinting..."
• NEWJun scRADAR: Dissecting intratumoral drug response heterogeneity at single-cell resolution via mechanism-guided prototype routing. (PLoS computational biology, 2026, PMID 42361193): "Post hoc attribution analyses highlighted candidate TGF-β-associated epithelial-to-mesenchymal transition signatures in Erlotinib-associated Resistant-labeled states and cytoskeletal/metabolic response-associated signatures in BET-inhibitor-associated Resistant-labeled states."
• NEWJun Paeoniae Decoction attenuates chronic colitis-associated intestinal fibrosis by suppressing TGF-β/Smad-mediated epithelial-mesenchymal transition and remodeling the metabolic microenvironment. (Journal of ethnopharmacology, 2026, PMID 42341856): "by suppressing TGF-β/Smad-mediated epithelial-mesenchymal transition and remodeling the metabolic microenvironment."
• NEWJun Endothelial Cell Phenotypic Plasticity in Atherosclerosis. (Handbook of experimental pharmacology, 2026, PMID 42313121): "...notably TGF-β, together with Wnt/β-catenin, Notch, NF-κB/STAT3, and epigenetic regulators such as HDAC9, drive this process."
• NEWJun Qishen Yiqi Dripping Pills Alleviate Myocardial Ischemia-Reperfusion-Induced Fibrotic Injury by Inhibiting Fibroblast Activation via the Transforming Growth Factor-Beta/Periostin Pathway. (Journal of ethnopharmacology, 2026, PMID 42269799): "However, whether QSYQ regulates transforming growth factor-beta (TGF-β)/Periostin (Postn) signaling to inhibit fibroblast activation remains unclear."
• Jun Photo-crosslinked methacrylated hyaluronic acid-iPRF hydrogel-based microneedles for accelerated wound repair. (International journal of biological macromolecules, 2026, PMID 42229655): "The hybrid patches exhibited controlled swelling and enzymatic degradation, which facilitated the sustained release of transforming growth factor-β (TGF-β) in vitro."
• Jun Growth arrest of thoracic aortic aneurysms in aging Marfan mice. (American journal of physiology. Heart and circulatory physiology, 2026, PMID 42222959): "Although there is a need to better understand the interconnected roles of temporal changes in differential gene expression and protein abundance, modulating transforming growth factor-beta (TGF-β) signaling and reducing mTOR signaling appear to merit increased attention in limiting aneurysmal expansion in Marfan syndrome."
• Jun Chitosan nanoparticles-incorporated polylactic acid/tacrolimus nanofiber composite membrane for tracheal scar inhibition and tracheal wound healing promotion. (International journal of biological macromolecules, 2026, PMID 42107578): "while suppressing hypertrophic scar fibroblast proliferation and collagen production by downregulating transforming growth factor-β and α-smooth muscle actin."
• Jun Ficerafusp Alfa (BCA101) With Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Two-Year Results of an Expansion Cohort of a Phase I/Ib Trial. (Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2026, PMID 42102329): "...in which elevated epidermal growth factor receptor and transforming growth factor-β impair tumor penetration of immune cells and lessen immunotherapy responses."