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Oral TGF-βR1 inhibitor Vactosertib promotes osteosarcoma regression by targeting tumor proliferation and enhancing anti-tumor immunity
Osteosarcoma (OS) is an aggressive malignant bone cancer, with refractory and metastatic disease remaining a significant challenge. Transforming growth factor-β1 (TGF-β) is a potent immune suppressive cytokine in OS and the TGF-β is increased in the sera of OS patients and this increase is associate...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104208/ https://www.ncbi.nlm.nih.gov/pubmed/37066414 http://dx.doi.org/10.21203/rs.3.rs-2709282/v1 |
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author | Choi, Sung Hee Myers, Jay Tomchuck, Suzanne Bonner, Melissa Eid, Saada Kingsley, Daniel VanHeyst, Kristen Kim, Seong-Jin Kim, Byung-Gyu Huang, Alex Y. |
author_facet | Choi, Sung Hee Myers, Jay Tomchuck, Suzanne Bonner, Melissa Eid, Saada Kingsley, Daniel VanHeyst, Kristen Kim, Seong-Jin Kim, Byung-Gyu Huang, Alex Y. |
author_sort | Choi, Sung Hee |
collection | PubMed |
description | Osteosarcoma (OS) is an aggressive malignant bone cancer, with refractory and metastatic disease remaining a significant challenge. Transforming growth factor-β1 (TGF-β) is a potent immune suppressive cytokine in OS and the TGF-β is increased in the sera of OS patients and this increase is associated with high-grade OS and lung metastases. Therefore, blocking TGF-β1 signaling may be a novel therapy for OS treatment. Here we show that blocking TGF-β1 signaling using TGF-βR1 inhibitor, Vactosertib, significantly inhibited OS proliferation in vitro and in vivo. Notably, Vactosertib inhibits c-Myc expression in the OS cells. Vactosertib increased immune effectors (IFNγ(+)CD8(+) cells and NK cells) and inhibited immune suppressors (M2-like TAM, MDSC) in the OS tumor microenvironment. Our results suggest that inhibition of TGF-β1 signaling is an effective therapeutic strategy against OS through a multi-pronged approach that targets tumor intrinsic and extrinsic factors to achieve optimal immune-effector functions and maximal clinical response. |
format | Online Article Text |
id | pubmed-10104208 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
spelling | pubmed-101042082023-04-15 Oral TGF-βR1 inhibitor Vactosertib promotes osteosarcoma regression by targeting tumor proliferation and enhancing anti-tumor immunity Choi, Sung Hee Myers, Jay Tomchuck, Suzanne Bonner, Melissa Eid, Saada Kingsley, Daniel VanHeyst, Kristen Kim, Seong-Jin Kim, Byung-Gyu Huang, Alex Y. Res Sq Article Osteosarcoma (OS) is an aggressive malignant bone cancer, with refractory and metastatic disease remaining a significant challenge. Transforming growth factor-β1 (TGF-β) is a potent immune suppressive cytokine in OS and the TGF-β is increased in the sera of OS patients and this increase is associated with high-grade OS and lung metastases. Therefore, blocking TGF-β1 signaling may be a novel therapy for OS treatment. Here we show that blocking TGF-β1 signaling using TGF-βR1 inhibitor, Vactosertib, significantly inhibited OS proliferation in vitro and in vivo. Notably, Vactosertib inhibits c-Myc expression in the OS cells. Vactosertib increased immune effectors (IFNγ(+)CD8(+) cells and NK cells) and inhibited immune suppressors (M2-like TAM, MDSC) in the OS tumor microenvironment. Our results suggest that inhibition of TGF-β1 signaling is an effective therapeutic strategy against OS through a multi-pronged approach that targets tumor intrinsic and extrinsic factors to achieve optimal immune-effector functions and maximal clinical response. American Journal Experts 2023-04-03 /pmc/articles/PMC10104208/ /pubmed/37066414 http://dx.doi.org/10.21203/rs.3.rs-2709282/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. https://creativecommons.org/licenses/by/4.0/License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License (https://creativecommons.org/licenses/by/4.0/) |
spellingShingle | Article Choi, Sung Hee Myers, Jay Tomchuck, Suzanne Bonner, Melissa Eid, Saada Kingsley, Daniel VanHeyst, Kristen Kim, Seong-Jin Kim, Byung-Gyu Huang, Alex Y. Oral TGF-βR1 inhibitor Vactosertib promotes osteosarcoma regression by targeting tumor proliferation and enhancing anti-tumor immunity |
title | Oral TGF-βR1 inhibitor Vactosertib promotes osteosarcoma regression by targeting tumor proliferation and enhancing anti-tumor immunity |
title_full | Oral TGF-βR1 inhibitor Vactosertib promotes osteosarcoma regression by targeting tumor proliferation and enhancing anti-tumor immunity |
title_fullStr | Oral TGF-βR1 inhibitor Vactosertib promotes osteosarcoma regression by targeting tumor proliferation and enhancing anti-tumor immunity |
title_full_unstemmed | Oral TGF-βR1 inhibitor Vactosertib promotes osteosarcoma regression by targeting tumor proliferation and enhancing anti-tumor immunity |
title_short | Oral TGF-βR1 inhibitor Vactosertib promotes osteosarcoma regression by targeting tumor proliferation and enhancing anti-tumor immunity |
title_sort | oral tgf-βr1 inhibitor vactosertib promotes osteosarcoma regression by targeting tumor proliferation and enhancing anti-tumor immunity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104208/ https://www.ncbi.nlm.nih.gov/pubmed/37066414 http://dx.doi.org/10.21203/rs.3.rs-2709282/v1 |
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