Inhibiting efferocytosis reverses macrophage-mediated immunosuppression in the leukemia microenvironment.

ABSTRACT:

Background

Previous studies show that the spleen and bone marrow can serve as leukemia microenvironments in which macrophages play a significant role in immune evasion and chemoresistance. We hypothesized that the macrophage driven tolerogenic process of efferocytosis is a major contributor to the immunosuppressive leukemia microenvironment and that this was driven by aberrant phosphatidylserine expression from cell turnover and cell membrane dysregulation.

Methods

Since MerTK is the prototypic efferocytosis receptor, we assessed whether the MerTK inhibitor MRX2843, which is currently in clinical trials, would reverse immune evasion and enhance immune-mediated clearance of leukemia cells.

Results

We found that inhibition of MerTK decreased leukemia-associated macropha

SUBMITTER: Cruz Cruz J 

PROVIDER: S-EPMC10027704 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature