Scientists have discovered a key reason why Small Cell Lung Cancer often resists immunotherapy. Their research shows that the tiny blood vessels around the tumor act like a barrier, preventing immune cells from entering the cancer and attacking it.
In theory, these tumors should be vulnerable to attack by Natural Killer cells because many small cell lung cancer cells hide from T cells by lowering their MHC class I signals. While NK cells can kill these cancer cells in laboratory experiments, researchers found that they are rarely present inside real patient tumors. Using advanced tumor models, the team discovered that the tumor’s micro-blood vessels block NK cells from leaving the bloodstream and reaching the cancer.
The study also found a possible way to overcome this barrier. Activating the STING pathway with a STING agonist can trigger an immune alarm that opens the blood vessel barrier, allowing NK cells to enter the tumor. The effect was even stronger when combined with CAR-NK cell therapy targeting DLL3, a protein commonly found on small cell lung cancer cells. Researchers say future treatments may focus not only on strengthening immune cells but also on helping them reach tumors more effectively.