New research from IRB Barcelona and CNAG uncovers how colorectal tumors build a powerful two-layer defense that shields them from the immune system. Through the hormone TGF-β, tumors block immune cells (T lymphocytes) from entering and expanding within the tumor—effectively turning the cancer “invisible” to treatment.
The study, published in Nature Genetics, shows that when TGF-β is inhibited, immune cells can flood the tumor and reignite their attack. The team also identified osteopontin, a macrophage-derived protein, as a secondary suppressor, offering a new drug target that could complement immunotherapy.
While direct TGF-β inhibitors carry toxicity risks, the researchers propose alternative ways to disarm this “dual barrier,” potentially transforming outcomes for patients with metastatic colorectal cancer, who rarely respond to immunotherapy today.