# Group 1 Innate Lymphoid Cell Dysregulation in Acute Myeloid Leukemia

> **NIH NIH F30** · OHIO STATE UNIVERSITY · 2024 · $53,974

## Abstract

PROJECT SUMMARY/ABSTRACT
Acute myeloid leukemia (AML) is a common and aggressive hematologic malignancy caused by a pathologic
expansion of immature myeloid cells. Despite significant research efforts spanning 50 years, the 5-year survival
rate in AML has remain relatively unchanged at <27.4%, underscoring the need for innovative approaches to
treatment. Natural killer (NK) cells are a member of the group 1 innate lymphoid cell (ILC) family that play a
pivotal role in the detection and elimination of leukemic cells. However, we and others have previously shown
that AML is able to inhibit NK cell maturation, promoting disease progression. Mechanistically, we have shown
that AML blasts are capable of secreting agonists for the aryl hydrocarbon receptor (AHR) transcription factor,
which inhibits NK cell maturation and function. Accumulating evidence suggests that AHR is required for the
maintenance of a related group 1 ILC subset termed an “ILC1.” Notably, ILC1s have been shown to be pro-
tumorigenic in solid tumor mouse models. Therefore, we hypothesize that AML is able to skew ILC populations
to suppress immune-surveillance by NK cells while promoting ILC1s. Preliminary data from our group support
this hypothesis by demonstrating that AML is capable of expanding ILC1 populations in a tissue-specific manner
in an AML mouse model. Furthermore, we predict that these ILC1s are functionally hyperactive in the setting of
AML and promote disease progression. Our long-term goal in this project is to determine how AML leads to
dysregulation of group 1 ILCs and to elucidate the downstream consequences on AML progression. Thus, our
aims are 1) to identify and characterize the mechanism(s) which promote ILC1 expansion in AML and 2) to
determine the functional consequences of expanded ILC1 populations in AML. To address these aims, we will
use a combination of ex vivo and in vivo studies. First, we will determine whether AML promotes ILC1 expansion
through interconversion from NK cells, skewing of ILC progenitors towards an ILC1 phenotype, and/or from direct
proliferation of ILC1s. We will also use transgenic mouse models to assess the contribution of Ahr and ILC1-
derived cytokines in promoting AML progression. By identifying these mechanisms, we will be able to better
target these pathways to restore group 1 ILC homeostasis and inform the development of future immune-based
therapies. This project represents a novel and innovative approach to targeted therapy in AML by focusing on
how leukemia targets ILC populations, an area which has been understudied to date. Successful completion of
these studies will fill in critical knowledge gaps of how ILCs are dysregulated in AML and how these cells can be
targeted therapeutically to improve patient survival.

## Key facts

- **NIH application ID:** 10746445
- **Project number:** 5F30CA250244-03
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Matthew Lordo
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 5
- **Project period:** 2022-01-03 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10746445

## Citation

> US National Institutes of Health, RePORTER application 10746445, Group 1 Innate Lymphoid Cell Dysregulation in Acute Myeloid Leukemia (5F30CA250244-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10746445. Licensed CC0.

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