Targeting myeloid-derived suppressor cells by inhibiting hypoxia-inducible factor 1α could improve tumor progression

Ann Med Surg (Lond). 2024 May 17;86(8):4449-4455. doi: 10.1097/MS9.0000000000002126. eCollection 2024 Aug.

Abstract

Myeloid-derived suppressor cells (MDSCs) are a subset of immature myeloid cells that inhibit anti-tumor immunity and contribute to poor cancer outcomes. In this study, the authors used multi-color flow cytometry to detect changes in MDSCs in patients with cancer and tumor-bearing mice. Then the authors studied changes in MDSCs ratio and mouse tumors after administration of hypoxia-inducible factor 1α (HIF-1α) inhibitor. The results showed that the ratio of MDSCs, specifically polymorphonuclear MDSCs (PMN-MDSCs), was higher in patients with cancer, and both PMN-MDSCs and monocytic MDSCs (M-MDSCs) ratio were higher in tumor-bearing mice. When provided with the HIF-1α inhibitor LW-6, the ratio of MDSCs decreased in tumor-bearing mice, particularly PMN-MDSCs, and the volume of liver metastases also decreased. The authors' findings suggest that reducing MDSCs by inhibiting hypoxia-inducible factor 1α may slow tumor progression.

Keywords: LW-6; cancer outcomes; hypoxia-inducible factor 1 α; myeloid-derived suppressor cells; tumor microenvironment.