Migrasome regulator TSPAN4 shapes the suppressive tumor immune microenvironment in pan-cancer.

BACKGROUND: Migrasomes are newly identified organelles on the retracting fibers of migrating cells, involved in releasing signaling molecules, expelling damaged mitochondria, and facilitating intercellular communication through phagocytosis. TSPAN4, a key regulator of migrasome formation, is a valuable marker for visualizing these organelles. However, its role in cancer remains unclear. METHODS: We analyzed TSPAN4 expression and its prognostic significance across multiple cancers using TCGA Pan-Cancer (PANCAN), and TCGA TARGET GTEx datasets. The relationship between TSPAN4 and tumor heterogeneity, stemness, and the immunosuppressive tumor microenvironment was explored through RNA-seq and scRNA-seq data. In addition, we examined TSPAN4's role in glioma, focusing on migrasome formation, cell proliferation, and macrophage polarization. RESULTS: Our analysis reveals that TSPAN4 is aberrantly expressed in various tumors, likely linked to its methylation status. It correlates with tumor heterogeneity, stemness, and a suppressive immune microenvironment. In glioma, TSPAN4 enhances cell proliferation and promotes macrophage polarization toward the immunosuppressive M2 phenotype. CONCLUSIONS: TSPAN4, as a migrasome regulator, plays a crucial role in shaping the immunosuppressive tumor microenvironment in pan-cancer.