{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:17:44Z","timestamp":1787026664795,"version":"build-2736575974"},"reference-count":134,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Transforming growth factor-\u03b2 (TGF-\u03b2) represents a family of multifunctional cytokines, primarily secreted by megakaryocytes, monocytes, T lymphocytes, bone marrow stromal cells, and other cell types. TGF-\u03b2 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-\u03b2 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-\u03b2 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-\u03b2 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-\u03b2 biosynthesis, activation, and signal transduction, discuss its functions across various immune cell types, and summarize recent progress and challenges in clinical research on TGF-\u03b2 targeted therapies for hematologic disorders, with the aim of providing new perspectives for related treatment strategies.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1728730","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T05:28:59Z","timestamp":1772083739000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["TGF-\u03b2 in hematologic malignancies: molecular functions and clinical applications"],"prefix":"10.3389","volume":"17","author":[{"given":"Ruiyang","family":"Li","sequence":"first","affiliation":[{"name":"The First Clinical Medical College, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengbo","family":"Yang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1926","article-title":"Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer","volume":"6","author":"Bierie","year":"2006","journal-title":"Nat Rev Cancer"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2010.04.002","article-title":"TGF-beta and immune cells: an important regulatory 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