ILC1s control leukemia stem cell fate and limit development of AML

How ILC1s respond to cancer cells is somewhat controversial. Here, the authors show that IFN gamma released by ILC1s can control acute myeloid leukemia by promoting leukemia stem cell apoptosis and favoring their differentiation into non-leukemic cells. Type I innate lymphoid cells (ILC1s) 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-gamma after cell-cell contact with LSCs, converge to suppress leukemogenesis in vivo. Conversely, the antileukemia potential of ILC1s wanes when JAK-STAT or PI3K-AKT signaling is inhibited. The relevant antileukemic properties of ILC1s are also functional in healthy individuals and impaired in individuals with acute myeloid leukemia (AML). Collectively, these findings identify ILC1s as anticancer immune cells that might be suitable for AML immunotherapy and provide a potential strategy to treat AML and prevent relapse of the disease.

Automated summary

ILC1s can control acute myeloid leukemia by promoting leukemia stem cell apoptosis and favoring their differentiation into non-leukemic cells through the production of interferon-gamma. These findings provide a potential strategy for AML immunotherapy.