Document Type

Article

Publication Date

11-17-2025

Comments

This article is the author's final published version in Blood Advances, Volume 9, Issue 12, November 2025, Pages 5888 - 5901.

The published version is available at https://doi.org/10.1182/bloodadvances.2025017018. Copyright © 2025 American Society of Hematology.

Abstract

The consequences of activated innate immune signaling in acute myeloid leukemia (AML) is not well understood. Using ligands directed at the toll-like family receptors (TLR) in models of high-risk AML, we uncover that TLR2 ligands exert unique antileukemic effects that are distinct from other TLRs. Although TLR2 signaling broadly induces inflammatory gene expression in AML cells, at the single-cell level, cell-type-dependent, divergent transcriptional responses coordinate cellular outputs of proliferation, differentiation, cell death, and activation of immune cell function. TLR2 ligands were the only TLR agonists capable of extending survival of AML-bearing mice through leukemia stem cell (LSC) reprogramming that elevated major histocompatibility complex (MHC) class II surface expression and ultimately impaired self-renewal. We find that the coexpression of TLR2 and MHCII genes is associated with better overall survival in patients with AML, which is consistent with our observations of activated TLR2 signaling in mice. These data reveal functional TLR2 signaling critically antagonizes leukemogenesis and emphasizes a role for TLR2 agonism in AML.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Language

English

Download

Share

COinS