TIPE regulates TGFB2 expression and induces extracellular M2 polarization in CRC

• DOI: 10.1093/jleuko/qiaf066
• Publication Date: 2025-05-20T10:45:16Z
• Authors: Qiang Zhu; Shiying Zhang; Changxiu Yan; Zeyang Lin; Shuaishuai Zhang; Haoyang Li; Yuhan Ye; Zhongchen Liu; Guohong Zhuang; Kun Zhang
• Keywords: Macrophage polarization

Abstract The immunosuppressive tumor microenvironment (TME) is a critical determinant of therapeutic resistance in colorectal cancer (CRC). TME encompasses diverse cellular and stromal elements, including cells, immune extracellular matrix (ECM), lymphatic vessels. Among these components, tumor-associated macrophages (TAMs) predominate both quantitatively functionally, with M2-polarized being the principal subset responsible for immunosuppression. Identifying genes that promote M2 polarization from CRC would provide more targeted approach to addressing this issue at its root. In study, we demonstrate TIPE derived indirectly stimulates polarization. Mechanistically, activates P38 MAPK signaling pathway, leading increased expression secretion TGFB2, which subsequently acts on induce Moreover, polarized by CRC-derived factors exert feedback loop enhances proliferation, migration, invasion, effect intensifying as increases. Animal experiments have also revealed TGFB2 induced can disseminate systemically via bloodstream, influencing not only peritumoral but inducing distant organs. Collectively, our findings indicate polarize an phenotype, thereby amplifying malignant behavior CRC.