LAMP2 drives M2 macrophage polarization and promotes glioma progression through autophagy.

Macrophages are abundant immune cells in the glioma microenvironment and are closely associated with cancer progression. Lysosome-associated membrane protein 2 (LAMP2) is a key regulator involved in the maturation of autophagolysosomes. This study employed scRNA-seq and bulk RNA-seq analyses to identify the potential role of LAMP2 in low-grade glioma (LGG) progression. In glioma cells, LAMP2 was upregulated, and lentiviral knockdown of LAMP2 significantly inhibited cell proliferation, migration and invasion, while increasing apoptosis. In vivo, LAMP2 knockdown suppressed tumor growth. Mechanistically, in glioma cells, LAMP2 silencing reduced autolysosome formation and impaired late-stage autophagic flux, supporting a role for LAMP2 in autophagolysosome maturation. In macrophages, LAMP2 expression was higher in M2-polarized cells, and LAMP2 overexpression enhanced M2 markers together with autophagic activity; autophagy inhibition by 3-MA attenuated these effects. Importantly, conditioned medium from LAMP2-overexpressing M2 macrophages promoted malignant phenotypes of glioma cells, supporting a macrophage-to-tumor pro-tumor effect. These findings highlight LAMP2 as a critical regulator of autophagy-mediated macrophage polarization and tumor progression, suggesting its potential as a prognostic biomarker and therapeutic target in LGG.