One property of cancer cells that can help them gain and maintain a foothold in the body is their ability to evade detection and destruction by the human immune system. Some tumor cells, for example, make higher-than-normal amounts of proteins called “don’t eat me” signals, which are found on the cell surface. These “don’t eat me” proteins are a type of immune checkpoint. They are “like invisibility cloaks for the cancer,” preventing white blood cells called macrophages from detecting, engulfing, and devouring the tumor cells, explained Irving Weissman, M.D., of Stanford University School of Medicine. In a new study, Dr. Weissman and his colleagues have discovered that a protein called CD24 is a new “don’t eat me” signal that they believe is a potential target for cancer immunotherapy. The team’s findings suggest that ovarian cancer and triple-negative breast cancer, both of which are notoriously hard to treat, are among the cancers that could be targeted by blocking CD24, said Amira Barkal, an M.D., Ph.D. student at Stanford and lead researcher on the new study, which was published July 31 in Nature. Further work is needed to better understand CD24’s role in human tumors and develop drugs that can block its activity, said Susan McCarthy, Ph.D., of NCI’s Division of Cancer Biology. But the study “provides real possibilities” that targeting CD24 might help a patient’s immune system act more strongly against certain cancers, including ovarian cancer and triple-negative breast cancer, for which immunotherapy has so far shown limited efficacy, Dr. McCarthy said. Most types of immunotherapy already in use target white blood cells called T cells, which are key components of the body’s second line of immune defense, known as adaptive immunity. By contrast, macrophages, whose action CD24 suppresses, are part of the innate immune system—the body’s first line of defense against infections and abnormal cells. The new findings, Dr. McCarthy said, are a reminder that macrophages, and not just T cells, can eliminate cancer cells.