dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | Gulley, James |
dc.contributor.author | Schlom, Jeffrey |
dc.contributor.author | Barcellos-Hoff, Mary Helen |
dc.contributor.author | Wang, Xiao-Jing |
dc.contributor.author | Seoane, Joan |
dc.contributor.author | Audhuy, Francois |
dc.date.accessioned | 2023-05-23T10:20:05Z |
dc.date.available | 2023-05-23T10:20:05Z |
dc.date.issued | 2022-06 |
dc.identifier.citation | Gulley JL, Schlom J, Barcellos-Hoff MH, Wang XJ, Seoane J, Audhuy F, et al. Dual inhibition of TGF-β and PD-L1: a novel approach to cancer treatment. Mol Oncol. 2022 Jun;16(11):2117–34. |
dc.identifier.issn | 1878-0261 |
dc.identifier.uri | https://hdl.handle.net/11351/9597 |
dc.description | Immune checkpoint inhibitor; Tumor microenvironment |
dc.description.abstract | Transforming growth factor-β (TGF-β) 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-β 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-β signaling in the TME is associated with resistance to these therapies. In this review, we discuss the importance of the TGF-β 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-βRII receptor (a TGF-β ‘trap’) fused to a human immunoglobulin G1 (IgG1) monoclonal antibody blocking PD-L1. Given the immunosuppressive effects of the TGF-β and PD-L1 pathways within the TME, colocalized and simultaneous inhibition of these pathways may potentially improve clinical activity and reduce toxicity. |
dc.language.iso | eng |
dc.publisher | Wiley |
dc.relation.ispartofseries | Molecular Oncology;16(11) |
dc.rights | Attribution 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ |
dc.source | Scientia |
dc.subject | Càncer - Tractament |
dc.subject | Anticossos monoclonals - Ús terapèutic |
dc.subject | Factors de creixement - Ús terapèutic |
dc.subject.mesh | Neoplasms |
dc.subject.mesh | /drug therapy |
dc.subject.mesh | Antibodies, Monoclonal |
dc.subject.mesh | Transforming Growth Factor beta |
dc.title | Dual inhibition of TGF-β and PD-L1: a novel approach to cancer treatment |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | 10.1002/1878-0261.13146 |
dc.subject.decs | neoplasias |
dc.subject.decs | /farmacoterapia |
dc.subject.decs | anticuerpos monoclonales |
dc.subject.decs | factor de crecimiento transformador beta |
dc.relation.publishversion | https://doi.org/10.1002/1878-0261.13146 |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
dc.contributor.organismes | Institut Català de la Salut |
dc.contributor.authoraffiliation | [Gulley JL] Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. [Schlom J] Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. [Barcellos-Hoff MH] Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA. [Wang XJ] Department of Pathology, University of Colorado, Aurora, CO, USA. [Seoane J] ICREA, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. CIBERONC, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Audhuy F] EMD Serono, Billerica, MA, USA |
dc.identifier.pmid | 34854206 |
dc.identifier.wos | 000738552600001 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |