Abstract

Glioma is a highly aggressive brain tumor characterized by a profoundly immunosuppressive tumor microenvironment dominated by M2-polarized tumor-associated macrophages (TAMs). This study utilized machine learning and single-cell multi-omics technologies to investigate the role of LILRB3 in glioma immunosuppression and evaluated the therapeutic potential of BM@nano-siLILRB3. In a tumor-bearing mouse model, core immune cells and key genes in glioma progression were identified. In vitro studies revealed that silencing LILRB3 suppressed M2 phenotypes in macrophages and inhibited glioma cell proliferation and invasion. In vivo experiments confirmed that LILRB3 promoted TAM M2 polarization, fostering an immunosuppressive microenvironment and accelerating glioma progression. The BM@nano-siLILRB3 nanoplatform effectively targeted the BBB, suppressed LILRB3 expression, reprogrammed immune responses, and led to substantial tumor growth inhibition. Overall, targeting LILRB3 with BM@nano-siLILRB3 shows promise in mitigating immunosuppression and hindering glioma progression, providing a novel therapeutic avenue for glioma treatment.