Human type-1 innate lymphoid cells control leukemia stem cell differentiation and limit acute myeloid leukemia development
Year: 2026
Type: article
Abstract: Innate lymphocytes can mediate cancer immunosurveillance and protect against disease. We have demonstrated that mouse type I innate lymphoid cells (ILC1s) can contribute to controlling the growth of acute myeloid leukemia (AML). However, the functional roles of human ILC1s in AML remain largely undefined. Here, we found that the ILC1s in patients with AML are impaired while a high expression of the ILC1 gene signature is associated with better overall survival in AML. By directly interacting with leukemia stem cells (LSCs), human ILC1s can eliminate LSCs via production of IFNγ and block LSC differentiation into M2 macrophage-like, leukemia-supporting cells through TNF. Collectively, these effects converge to limit leukemogenesis in vivo . We also identified Lin − CD127 + CD161 − CRTH2 − CD117 − cells as the human ILC1 subset. The use of umbilical cord blood (UCB) CD34 + hematopoietic stem cells to generate CD161 − ILC1s could allow for a readily available supply of ILC1s to be produced for human adoptive transfer studies. Together, our findings provide evidence that targeting human ILC1s may be a promising therapeutic approach for prolongation of disease-free survival in AML.
Source: Nature Communications
Language: English
Topic: IL-33, ST2, and ILC Pathways
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G1200741440, Overcoming Barriers of Virotherapy by Next-Generation oHSV Expressing E-Cadherin, G2397580644, G2557530977, G3887401773, Elucidate and Modulate Cell Signaling in NK Cells for Glioma Treatment, G5075107534, G5620728000, scFvPD1-FLT3 CAR T Cells for the Treatment of Relapsed Acute Myeloid Leukemia, G5936054862, G7605725088, G7955300722, G832265149, Characterizing and Targeting the Novel IL-15- AKT-XBP1s Pathway in NK Cells, G9000062509, G9000077798, G9000145997, G9000223019, G9000226092, G9000304435, Human natural killer cells: Advancing biology and clinical applications, Targeting FLT3 for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia, Development of Small Molecule Inhibitors and Biologic Agents for Treatment of Glioblastoma Using Intracerebral Microdialysis and Signatures of Vulnerability, Phase 1 Evaluation of Enhanced Natural Killer Cells as a Treatment Strategy in Non-Small cell Lung Cancer Patients Refractory to PD-1/PD-L1 Immune Checkpoint Inhibitors, Circumventing Barriers to Effective Oncolytic Virotherapy of Malignant Gliomas
OpenAlex ID: W7127918254