Targeting Trained Immunity for Tumor-Associated Macrophages with Engineered BCG Sensitizes Glioblastoma Radiotherapy

Radiotherapy (RT) resistance in glioblastoma (GBM) is driven by an immunosuppressive tumor microenvironment. We developed macrophage membrane-camouflaged BCG (MBCG) to target tumor-associated macrophages (TAMs) and induce trained immunity, enhancing RT efficacy. MBCG penetrates the blood-brain barrier, alleviates hypoxia via catalase activity, and reprograms TAMs to promote phagocytosis, cytokine release, and CD8+/NK cell recruitment. Combined with immune checkpoint blockade, MBCG+RT shows synergistic antitumor effects in murine and humanized GBM models. This study provides transcriptomic data (RNA-seq) of TAMs under MBCG+RT treatment, revealing mechanisms of trained immunity-mediated radiosensitization.