口服 TGF-βR1 抑制剂 Vactosertib 通过靶向肿瘤增殖和增强抗肿瘤免疫促进骨肉瘤消退

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.