Study Finds TGF-β Builds Dual Immune Barrier in Metastatic Colorectal Cancer

Overview

• Researchers show that TGF-β blocks recruitment of tumor-killing T cells from the bloodstream and programs macrophages to restrain the few T cells that enter.
• Macrophage-mediated suppression is linked to increased osteopontin production, which dampens intratumoral T cell expansion.
• Single-cell analyses across mouse liver-metastasis models and human metastatic samples mapped the cell types and signaling driving immune evasion.
• Pharmacologic blockade of TGF-β in preclinical models enabled massive T cell infiltration and, with checkpoint therapy, produced strong anti-tumor responses.
• Because systemic TGF-β inhibition has side effects, the authors prioritize safer, selective approaches—such as targeting osteopontin—for evaluation in combination trials.