Targeted Deletion of Peroxiredoxin 1 Enhances Anti-Tumor Immunity in Colorectal Cancer by Reprogramming the Immunosuppressive Tumor-Associated Macrophages.

ABSTRACT: Peroxiredoxin 1 (PRDX1) overexpression in colorectal cancer (CRC) correlates with poor prognosis and reduced T-cell infiltration. However, the mechanism underlying PRDX1-mediated immune suppression remains elusive. In this study, we found that knockout of PRDX1 robustly suppressed AOM/DSS-induced colonic adenocarcinoma compared with wild-type C57BL/6J mice, accompanied by highly infiltrated CD4⁺/CD8⁺ T cells and reduced CD163⁺ tumor-associated macrophages (TAMs). Furthermore, PRDX1 knockdown in CRC cells inhibited M2 macrophage polarization by impairing hypoxia-inducible factor 1α (HIF-1α)/GLUT-1-mediated glycolysis and lactate secretion. Mechanistically, PRDX1 binds to Cullin-2 as a molecular chaperone, thereby suppressing ubiquitination and degradation of

SUBMITTER: Sun Y 

PROVIDER: S-EPMC12644249 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature