TGF-β in hematologic malignancies: molecular functions and clinical applications

Transforming growth factor-β (TGF-β) represents a family of multifunctional cytokines, primarily secreted by megakaryocytes, monocytes, T lymphocytes, bone marrow stromal cells, and other cell types. TGF-β plays an essential role in various physiological processes, including the regulation of cell proliferation, differentiation, apoptosis, and immune homeostasis. As a key immunoregulatory cytokine, TGF-β contributes to an immunosuppressive network within the microenvironment of hematologic malignancies by modulating the functions of both adaptive and innate immune cells. Current studies have shown that TGF-β is often highly expressed in major hematologic malignancies such as leukemia, lymphoma, and multiple myeloma (MM). It not only enhances immunosuppression by inhibiting effector T cell activation but also regulates tumor cell proliferation, apoptosis, and drug resistance. Meanwhile, strategies targeting the TGF-β signaling pathway have shown potential to improve immunotherapy responses in preclinical models of hematologic malignancies. Several such agents have now entered early-phase clinical trials, offering a promising direction for enhancing the efficacy of immunotherapy in these diseases. In this review, we outline the molecular mechanisms of TGF-β biosynthesis, activation, and signal transduction, discuss its functions across various immune cell types, and summarize recent progress and challenges in clinical research on TGF-β targeted therapies for hematologic disorders, with the aim of providing new perspectives for related treatment strategies.