Galectin-9 promotes colon cancer development by polarizing macrophages toward the M2 phenotype

Galectin-9 plays multiple roles in various Tumors and exerts immune regulation within the tumor microenvironment. It is closely associated with tumor prognosis. This study aimed to analyze the expression of Galectin-9 in the colon tumor microenvironment. The results indicated that Galectin-9 expression is higher in the colon tumor microenvironment compared to adjacent normal tissues. Furthermore, high expression of Galectin-9 was related to M2-type Macrophages, which promote tumor development by increasing tumor cell viability, migration, and invasion. Notably, high expression of Galectin-9 in colon tumor microenvironment contributed to the polarization of M2 cells, marked by high expression of arginase-1, CD163, and IL-10 and low expression of iNOS. When M0 Macrophages were treated with Galectin-9 and co-cultured with colon Cancer cell lines, it resulted in increased Cancer cell growth, migration, and invasion by promoting the differentiation of THP-1 monocytes into the M2 Macrophages. The specific mechanism by which Galectin-9 promotes M2 polarization involves its binding to TIM-3, recruiting PI3K-p85 to the cytoplasmic domain of TIM-3. This interaction further affects the PI3K/Akt signal pathway, leading to M2 polarization.