Diet and gut microbes shape immunotherapy side-effect severity

University of Pittsburgh scientists identified fragile immune cells that drive a serious immunotherapy side effect and found that diet and gut microbiome composition can affect its severity. In mice, blocking a protein in those cells reversed the inflammation. The work was published in Cell.

The Pittsburgh team focused on immune-related adverse events tied to checkpoint inhibitors, drugs that release T-cell restraints so the immune system can attack tumors. Such treatment can also provoke healthy-tissue inflammation; severe cases occur in roughly a quarter of recipients and often lead to hospitalization or stopped therapy. No FDA-approved remedy exists for these reactions.

To study variability, researchers fed mice a low-fiber, high-fat, processed-carbohydrate diet before and during treatment, producing a model that mirrored human immune and microbiome features without full gene knockouts. Combining that model with patient data pointed to a protein in unstable immune cells; disabling it in mice reduced inflammation.