Related Experiment Video
Updated: Jan 19, 2026
Evaluation of Tumor-infiltrating Leukocyte Subsets in a Subcutaneous Tumor Model
Published on: April 13, 2015
Controlling the Phenotype of Tumor-Infiltrating Macrophages via the PHD-HIF Axis Inhibits Tumor Growth in a Mouse
Shunji Nishide1, Shinji Matsunaga2, Masayuki Shiota3
1Department of Pharmacology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan; Department of Urology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
Abstract:
The tumor microenvironment (TME) polarizes tumor-infiltrating macrophages toward tumor support. Macrophage-abundant tumors are highly malignant and are the cause of poor prognosis and therapeutic resistance. In this study, we show that the prolyl hydroxylase (PHD) inhibitor FG-4592 (FG) inhibits tumor growth of macrophage-abundant tumors and prolongs mouse survival. FG not only normalizes tumor vessels and improves tumor oxygenation but also directly affects macrophages and activates phagocytosis through the PHD-hypoxia-inducible factor (HIF) axis. Remarkably, FG can promote phagocytic ability of the Ly6Clo subset of tumor-infiltrating macrophages, leading to tumor growth inhibition. Moreover, Ly6Cneg macrophages contributed to blood vessel normalization. Using a malignant tumor mouse model, we characterized macrophage function and subsets. Altogether, our findings suggest that the PHD inhibitor can promote the anti-tumor potential of macrophages to improve cancer therapy.
Insights
The prolyl hydroxylase (PHD) inhibitor FG-4592 effectively inhibits malignant tumor growth by enhancing macrophage anti-tumor activity. This drug normalizes tumor blood vessels and boosts macrophage phagocytosis, improving cancer therapy outcomes.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Tumor microenvironment (TME) promotes macrophage polarization towards tumor support.
- Macrophage-rich tumors exhibit high malignancy, poor prognosis, and therapeutic resistance.
Purpose of the Study:
- To investigate the efficacy of the prolyl hydroxylase (PHD) inhibitor FG-4592 (FG) in treating macrophage-abundant tumors.
- To elucidate the mechanisms by which FG affects tumor-infiltrating macrophages and tumor growth.
Main Methods:
- Utilized a malignant tumor mouse model to study macrophage function and subsets.
- Administered FG-4592 and analyzed its effects on tumor growth, vascularization, oxygenation, and macrophage subsets (Ly6C lo and Ly6C neg ).
- Investigated the PHD-hypoxia-inducible factor (HIF) axis in FG-mediated macrophage activation.
Main Results:
- FG-4592 significantly inhibited tumor growth and prolonged survival in mice with macrophage-abundant tumors.
- FG treatment normalized tumor vasculature and improved tumor oxygenation.
- FG enhanced the phagocytic capacity of Ly6C lo tumor-infiltrating macrophages and promoted blood vessel normalization via Ly6C neg macrophages.
Conclusions:
- The PHD inhibitor FG-4592 demonstrates potent anti-tumor effects in macrophage-abundant tumors.
- FG activates macrophages, particularly the Ly6C lo subset, enhancing their anti-tumor functions.
- Targeting the PHD-HIF axis with inhibitors like FG-4592 offers a promising strategy to improve cancer immunotherapy by modulating macrophage activity.
Related Concept Videos
07:49Evaluation of Tumor-infiltrating Leukocyte Subsets in a Subcutaneous Tumor Model
07:02In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
08:42Establishment of a Co-culture System of Patient-Derived Colorectal Tumor Organoids and Tumor-Infiltrating Lymphocytes (TILs)
07:36Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
06:35A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
02:02A Three-Dimensional Co-culture Model of Infiltrating T Cells in Tumor Spheroids