Oral TGF-βR1 inhibitor Vactosertib promotes osteosarcoma regression by targeting tumor proliferation and enhancing anti-tumor immunity.

ABSTRACT: 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 mic

SUBMITTER: Choi SH 

PROVIDER: S-EPMC10104208 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature