Cyclophilin J Reprograms Tumor-associated Macrophages to Exert an Anti-tumor Effect in Liver Cancer

作者：Jing Wang, Chen Yao, Qi Zeng, Li‐Xia Peng, Shimeng Zhang, Yizhi Mao, Lingyi Fu, Shuai Chen, Chunjie Sheng · 发表于：International Journal of Biological Sciences · 年份：2025 · DOI：10.7150/ijbs.113197 · 被引用次数：2 · 研究领域：Signaling Pathways in Disease、Synthesis of Tetrazole Derivatives、RNA Interference and Gene Delivery

The presence of tumor-associated macrophages (TAMs) characterized by an M2-like phenotype sustains a robust immunosuppressive tumor microenvironment (TME), promoting liver hepatocellular carcinoma (LIHC) progression.Here, we find that genetic deletion of cyclophilin J (CYPJ) in mice significantly accelerates the development of liver cancer.Analysis of immune cell infiltration reveals that high expression of CYPJ correlates with an increased proportion of M1-polarized, anti-tumor macrophages and CD8 + T cells in the TME.Mechanistically, we demonstrate that CYPJ interacts with AKT1 and inhibits the PI3K-AKT signaling pathway, which leads to polarization of TAMs toward the anti-tumor M1 phenotype, resulting in a tumor-suppressive effect.Collectively, our findings implicate CYPJ as a novel potential therapeutic target for macrophage-mediated therapy in liver cancer.