The Perils and Promise of Cellular Cannibalism in Development, Homeostasis, and Disease

Cellular cannibalism, defined as one cell eating another, is a widespread cellular behavior in organisms ranging from flies and worms to fish and mammals, where it is essential for development and homeostasis. Some cells nibble on other cells in a process called trogocytosis or grooming. Alternatively, cells can engulf other cells whole, as when macrophages consume stressed stem cells or aged red blood cells. Excessive cellular cannibalism can lead to degenerative disease or immunodeficiency, and cancer cells can hijack this normal behavior to fuel their growth and evade immune attack. Next-generation immunotherapies aim to harness cannibalistic behavior to combat cancer and other diseases, including atherosclerosis. Chimeric antigen receptor macrophage (CAR-M) therapies are in clinical trials for cancer. Elucidating the molecular and cellular mechanisms that drive physiological and pathological cellular cannibalism is likely to inform efforts to improve CAR-M and other therapies that depend on antibody-dependent cellular phagocytosis and tumor-associated macrophage reprogramming.