ILC1s Control Leukemia Stem Cell Fate and Limit Development of AML

Type I innate lymphoid cells (ILC1) are critical regulators of inflammation and immunity in mammalian tissues. However, their function in cancer is mostly undefined. Here we show that a high density of ILC1s induces leukemia stem cell (LSC) apoptosis in mice. At a lower density, ILC1s prevent LSCs from differentiating into leukemia progenitors and promote their differentiation into non-leukemic cells, thus blocking the production of terminal myeloid blasts. All of these effects, which require ILC1s to produce interferon-γ after cell–cell contact with LSCs, converge to suppress leukemogenesis in vivo. Conversely, the anti-leukemia potential of ILC1s wanes when JAK-STAT or PI3K-AKT signaling is inhibited. The relevant anti-leukemic properties of ILC1s are also functional in healthy people and impaired in patients with acute myeloid leukemia (AML). Collectively, these findings identify ILC1s as anti-cancer immune cells that might be suitable for AML immunotherapy, and provide a potential strategy to treat AML and prevent relapse of the disease.