Work

Myeloid-lineage-specific membrane protein LRRC25 suppresses immunity in solid tumor and is a potential cancer immunotherapy checkpoint target

Year: 2025

Type: article

Abstract: Leucine-rich repeat containing 25 (LRRC25), a type I membrane protein, is specifically expressed in myeloid cells including neutrophils and macrophages. The anti-inflammatory role of LRRC25 was suggested in a few pathogenic models. However, its role in cancer immunity has not been interrogated. Here, we demonstrate that LRRC25 is robustly expressed in tumor-associated macrophages (TAMs). Lrrc25 deficiency in the tumor microenvironment (TME) suppresses growth of multiple murine tumor models by reprogramming TAMs toward an anti-tumor phenotype and thereby enhancing infiltration and activation of CD8 + T cells. The Nox2-ROS-Nlrp3-Il1β pathway is elevated in Lrrc25 -deficient TAMs. Furthermore, a human myeloid cell line or mice with loss of Lrrc25 appear normal, indicating that LRRC25 is a safe immune target. Our results suggest that as an unappreciated immune checkpoint for tumor immunotherapy, the myeloid-specific membrane protein LRRC25 orchestrates the activity of TAMs via the canonical Nlrp3-IL1β inflammatory pathway and influences CD8 + T cell chemotaxis to the TME.

Source: Cell Reports

DOI: 10.1016/j.celrep.2025.115631

Authors: Guorong Zhang, Hanzhi Yu, Jingjing Liu, Ge Dong, Zhigang Cai

Institutions: State Key Laboratory of Experimental Hematology, Tianjin Medical University, Tianjin Medical University General Hospital

Language: English

Topic: Immune cells in cancer

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,620