Language

English

Publication Date

12-15-2023

Journal

Cancer Research

DOI

10.1158/0008-5472.CAN-22-2483

PMID

38098451

PMCID

PMC11932437

PubMedCentral® Posted Date

3-24-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Identifying novel cell surface receptors that regulate leukemia cell differentiation and can be targeted to inhibit cellular proliferation is crucial to improve current treatment modalities in acute myeloid leukemia (AML), especially for relapsed or chemotherapy-refractory leukemia. Leukocyte immunoglobulin-like receptor type B (LILRB) is an immunomodulatory receptor originally found to be expressed in myeloid cells. In this study, we found that LILRB receptors can be induced under inflammatory stimuli and chemotherapy treatment conditions. Blockade of LILRB3 inhibited leukemia cell proliferation and leukemia progression. Additionally, treatment with LILRB3 blocking antibodies upregulated myeloid lineage differentiation transcription factors, including PU.1, C/EBP family, and IRF, whereas phosphorylation of proliferation regulators, e.g., AKT, cyclin D1, and retinoblastoma protein (Rb), was decreased. Conversely, transcriptomic analysis showed LILRB3 activation by agonist antibodies may enhance leukemia survival through upregulation of cholesterol metabolism, which has been shown to promote leukemia cell survival. Moreover, LILRB3-targeted CAR T cells exhibited potent antitumor effects both in vitro and in vivo. Taken together, our results suggest that LILRB3 is a potentially potent target for multiple treatment modalities in AML.

Keywords

Humans, Immunotherapy, Adoptive, T-Lymphocytes, Leukemia, Myeloid, Acute, Receptors, Cell Surface, Myeloid Cells, Receptors, Immunologic, Antigens, CD

Published Open-Access

yes

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