Targeting new innate immune evasion mechanisms in acute myeloid leukemia

Acute myeloid leukemia (AML) arises from hematopoietic stem and progenitor cells and is associated with poor survival.

For the disease to develop, the AML cells need to escape tumor immune surveillance, but the mechanistic basis for this is mostly unknown.

This project is based on our recent discoveries of cell surface proteins on AML cells that suppress innate immune cells. By CRISPR screening, we found that SLC3A2 inhibition in AML cells sensitizes them for Natural killer (NK) cell killing. Moreover, we found that inhibition of MFSD2A or SCARB2 sensitize AML cells for macrophage-mediated phagocytosis.

By mechanistically characterizing how these cell surface proteins on AML suppress NK cells and macrophages, and measure their expression pattern in AML, we will explore them as new therapeutic targets.

In particular, we will evaluate therapeutic effects of inhibiting them ex vivo and in leukemia mouse models using antibodies. I will perform this project together with two postdocs, one PhD student and one biomedical scientist.

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 treatments for AML patients and possibly other cancers.