Work

Magrolimab (Hu5F9-G4) promotes macrophage M1 polarization and is associated with enhanced autophagy in colorectal cancer

Year: 2025

Type: article

Abstract: • High M2d macrophage infiltration correlates with poor prognosis in colorectal cancer (CRC). • Hu5F9-G4 promotes M2d-to-M1 macrophage polarization, inhibits CRC cell proliferation and migration, and enhances autophagy in macrophages. • In vivo studies show that Hu5F9-G4 reduces tumor growth and modulates immune cell populations in CRC-bearing mice. • Integrative analyses identify CDKN1A and MAP1LC3B as potential therapeutic targets associated with the autophagy pathway. • Hu5F9-G4 has therapeutic potential in CRC by modulating macrophage polarization, tumor progression, and autophagy-related pathways. The role of macrophage infiltration in colorectal cancer (CRC) and its implications for prognosis remains uncertain. While macrophage immune checkpoint inhibitors have shown efficacy in treating solid tumors, their impact on CRC progression and immune regulation is unclear. This study investigates the effect of the macrophage immune checkpoint inhibitor Hu5F9-G4 on the immune microenvironment, macrophage behaviour, and CRC progression to identify potential therapeutic targets. A total of 73 CRC samples were analysed to evaluate the association between M2d macrophage infiltration and prognosis. In vitro studies examined the effect of Hu5F9-G4 on M2d-to-M1 polarization, CRC cell proliferation, and migration. In vivo experiments assessed tumor growth and macrophage polarization in CRC-bearing mice treated with Hu5F9-G4. Single-cell transcriptome analysis, bioinformatics, and clinical validations were conducted to identify potential autophagy-related therapeutic targets. High M2d macrophage infiltration correlated with poor CRC prognosis. Hu5F9-G4 treatment significantly promoted M2d-to-M1 polarization, inhibited CRC cell proliferation and migration, and increased autophagy in macrophages. In vivo, Hu5F9-G4 reduced tumor growth and modified immune cell populations. Integrative analyses identified CDKN1A and MAP1LC3B as potential therapeutic targets linked to the autophagy pathway. Hu5F9-G4 demonstrates potential as a therapeutic agent in CRC by promoting M2d-to-M1 macrophage polarization, suppressing tumor progression, and influencing the autophagy pathway. These findings highlight CDKN1A and MAP1LC3B as promising targets for CRC therapy.

Source: Translational Oncology

DOI: 10.1016/j.tranon.2025.102598