Identification and functional characterization of innate immune checkpoint regulators in acute myeloid leukemia
Description: Acute myeloid leukemia (AML) arises from hematopoietic stem and progenitor cells and is associated with exceedingly poor survival. For the disease to develop, the AML cells need to escape immune surveillance, but the mechanistic basis for this is unknown. The goal of this project is to provide a more effective treatment for AML by unleashing the innate immune system against the AML cells. I will pursue this goal by first identifying and mechanistically characterizing cell surface proteins on AML cells that suppress Natural killer (NK) cells and macrophages. To identify such cell surface proteins, which serve as innate immune checkpoints, I will pioneer unique in vivo and ex vivo CRISPR screens that we have developed within my research group. I will then characterize the function and expression patterns of the identified innate immune checkpoint regulators, and evaluate therapeutic effects of inhibiting them in leukemia mouse models. In particular, I will develop tools to target a chemotherapy-resistant cell population of leukemia cells with the ability to self-renew, a population termed leukemic stem cells. I will perform this project together with two postdocs and one PhD student. Successful completion of this research program will increase our understanding of how AML cells suppress the innate immune system, and will provide initial validations of therapeutic potential, findings that may translate into new and more effective antibody-based therapies for AML patients.
Funder: Vetenskapsrådet
Amount: SEK 4,800,000
Funding type: research
Funder scheme: Project grant
Start date: 2020-01-01
End date: 2023-12-31
Investigator: Marcus Järås
Institution: Lund University
Funded outputs count: 6
Funder award ID: 2019-01076
OpenAlex ID: G3033766832