2. Academic Validation
  3. Leukemia-driven expansion of type 3 innate lymphoid cell facilitates a pro-tumoral microenvironment in acute myeloid leukemia

Leukemia-driven expansion of type 3 innate lymphoid cell facilitates a pro-tumoral microenvironment in acute myeloid leukemia

  • Leukemia. 2025 Dec 22. doi: 10.1038/s41375-025-02829-7.
Thanh Thanh T Dinh # 1 2,  Matthew R Lordo # 1 2 3,  Amy Y Zhang 1 2 3,  Chinmayee Goda 4,  Nikolas Shilo 2,  Ekaterina Altynova 2,  Michael Ruesch 1 2 3,  Parker Kronen 2,  Megan Broughton 2,  Erin Jeremy 1 2 3,  Victoria L Sellers 2,  Xiaoli Zhang 5,  Karilyn T Larkin 2 6,  Patrick L Collins 2 7,  Adrienne M Dorrance 4,  Aharon G Freud 2 8,  Christopher C Oakes 2 5 6,  Bethany L Mundy-Bosse 9 10 11
Affiliations

Affiliations

  • 1 Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH, USA.
  • 2 The Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
  • 3 The Medical Scientist Training Program, The Ohio State University, Columbus, OH, USA.
  • 4 Department of Internal Medicine, University of Utah Health, Salt Lake City, UT, USA.
  • 5 Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.
  • 6 Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
  • 7 Department of Microbial Infection and Immunity, Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, OH, USA.
  • 8 Department of Pathology, The Ohio State University, Columbus, OH, USA.
  • 9 The Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA. [email protected].
  • 10 Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA. [email protected].
  • 11 Department of Microbial Infection and Immunity, Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, OH, USA. [email protected].
  • # Contributed equally.
PMID: 41430399 DOI: 10.1038/s41375-025-02829-7
Abstract

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with poor overall survival. Understanding how dysregulated immunity contributes to the development and progression of AML is an active area of investigation. Prior work has demonstrated functional defects in natural killer (NK) cells; however, the role of non-NK innate lymphoid cells (ILCs) in AML is incompletely understood. Conventional ILC3s are non-cytotoxic and regulate mucosal immunity through cytokine secretion. In this study, we discovered an expansion of ILC3s in both a murine model of AML and in AML patients. The transcription factor, Aryl Hydrocarbon Receptor (AHR) is required for ILC3 development and function, and AML blasts have been shown to secrete AHR ligands. Modeling studies demonstrated ILC3 expansion was mediated by AHR activation in ILC precursors. ILC3s developed in leukemic settings had increased cytokine production, and co-culture of ILC3s significantly increased AML colony formation, which was mediated by ILC3-derived TNFα and GM-CSF. Furthermore, co-transfer of ILC3s with AML led to more rapid disease progression in vivo and human ILC3 frequency was associated with adverse risk stratification in AML patients. These data support a model in which AML promotes ILC3 expansion and function via an AHR-dependent mechanism to aid AML growth and survival.

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