{"entity": "researcher", "timestamp": "2026-08-22T06:56:37.601Z", "family": "Gulley", "given": "James L", "initials": "JL", "orcid": "0000-0002-6569-2912", "affiliations": ["Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/d63fe5ffd4944a6287132bc7dfcb9486.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/d63fe5ffd4944a6287132bc7dfcb9486"}}, "publications": [{"entity": "publication", "iuid": "1a1d67c718fe453d947beb4231d7c1e6", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1a1d67c718fe453d947beb4231d7c1e6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1a1d67c718fe453d947beb4231d7c1e6"}}, "title": "Dual inhibition of TGF-\u03b2 and PD-L1: a novel approach to cancer treatment.", "authors": [{"family": "Gulley", "given": "James L", "initials": "JL", "orcid": "0000-0002-6569-2912", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d63fe5ffd4944a6287132bc7dfcb9486.json"}}, {"family": "Schlom", "given": "Jeffrey", "initials": "J"}, {"family": "Barcellos-Hoff", "given": "Mary Helen", "initials": "MH"}, {"family": "Wang", "given": "Xiao-Jing", "initials": "XJ"}, {"family": "Seoane", "given": "Joan", "initials": "J"}, {"family": "Audhuy", "given": "Francois", "initials": "F"}, {"family": "Lan", "given": "Yan", "initials": "Y"}, {"family": "Dussault", "given": "Isabelle", "initials": "I"}, {"family": "Moustakas", "given": "Aristidis", "initials": "A", "orcid": "0000-0001-9131-3827", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f11771bffabf4da6a2a5e2668c7c7c2d.json"}}], "type": "journal article", "published": "2022-06-00", "journal": {"title": "Mol Oncol", "issn": "1878-0261", "volume": "16", "issue": "11", "pages": "2117-2134", "issn-l": "1574-7891"}, "abstract": "Transforming growth factor-\u03b2 (TGF-\u03b2) and programmed death ligand 1 (PD-L1) initiate signaling pathways with complementary, nonredundant immunosuppressive functions in the tumor microenvironment (TME). In the TME, dysregulated TGF-\u03b2 signaling suppresses antitumor immunity and promotes cancer fibrosis, epithelial-to-mesenchymal transition, and angiogenesis. Meanwhile, PD-L1 expression inactivates cytotoxic T cells and restricts immunosurveillance in the TME. Anti-PD-L1 therapies have been approved for the treatment of various cancers, but TGF-\u03b2 signaling in the TME is associated with resistance to these therapies. In this review, we discuss the importance of the TGF-\u03b2 and PD-L1 pathways in cancer, as well as clinical strategies using combination therapies that block these pathways separately or approaches with dual-targeting agents (bispecific and bifunctional immunotherapies) that may block them simultaneously. Currently, the furthest developed dual-targeting agent is bintrafusp alfa. This drug is a first-in-class bifunctional fusion protein that consists of the extracellular domain of the TGF-\u03b2RII receptor (a TGF-\u03b2 'trap') fused to a human immunoglobulin G1 (IgG1) monoclonal antibody blocking PD-L1. Given the immunosuppressive effects of the TGF-\u03b2 and PD-L1 pathways within the TME, colocalized and simultaneous inhibition of these pathways may potentially improve clinical activity and reduce toxicity.", "doi": "10.1002/1878-0261.13146", "pmid": "34854206", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9168966"}], "notes": [], "created": "2026-08-20T06:26:44.107Z", "modified": "2026-08-20T06:26:44.180Z"}]}