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. 2024 Jul 22;9:176. doi: 10.1038/s41392-024-01868-3

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 7 — TGF-β signaling in cancer and TGF-β blockade for immunotherapy. The top panel illustrates the TGF-β signaling pathway in cancer cells, including the canonical Smad-dependent pathway and the non-canonical pathways involving various intracellular mediators such as MAPK, PI3K/Akt, and mTOR, leading to cellular processes like EMT, stemness, metastasis, treatment resistance, angiogenesis, and immune evasion. The bottom left panel depicts the role of TGF-β in the tumor microenvironment (TME), highlighting its immunosuppressive effects that facilitate cancer immune escape by interacting with various immune cells such as Treg, MDSC, M1/M2 macrophages, DC, NK, and CTL. The bottom right panel presents a schematic representation of innovative anti-TGF-β/PD-L1 therapeutic agents, demonstrating dual blockade strategies, as exemplified by M7824/SHR-1701, which combines a TGF-β trap with an anti-PD-L1 moiety, and YM101/BITP, which features both anti-TGF-β and anti-PD-L1 moieties for enhanced immunotherapy efficacy. Adapted from “Canonical and Non-canonical TGF-β Pathways in EMT”, by BioRender.com (2024). Retrieved from https://app.biorender.com/biorender-templates