St. Jude Children’s Research Hospital scientists have discovered how tumors disable immune “gatekeeper” cells that alert the rest of the immune system to the presence of cancer—and how restoring their energy production can improve immunotherapy. Dendritic cells activate the cytotoxic immune cells that destroy cancer. The researchers found that tumors reduce dendritic cell function by decreasing their mitochondrial fitness, thus preventing formation of the anticancer immune response.

The results, published in Science, also show that boosting mitochondrial function in dendritic cells enhances antitumor immune activity and strengthens the efficacy of existing immunotherapies.

Dendritic cells alert and activate tumor-killing immune cells as a critical part of anticancer immune response. However, within the nutrient-sparse tumor microenvironment (the complex mixture of chemicals, cells and other factors near cancer cells), dendritic cells progressively lose their energy-producing mitochondrial activity. That loss drives dendritic cell dysfunction and weakens the body’s immune defenses against cancer.