CELL INTELLIGENCE · 肿瘤细胞治疗研究

Acute Myeloid Leukemia (AML) is characterized by significant immunosuppression, limiting the efficacy of immunotherapy. Monocytic AML presents unique immunosuppressive features and constitutes a challenging subtype necessitating focused investigation. Using single-cell multi-omics analyses of primary AML samples, we revealed the immunosuppression landscape of monocytic AML and identified BLVRB as a marker of immunosuppressive monocytic AML cells. BLVRB depletion downregulated immune-modulatory gene expression and sensitized AML cells to T cell cytotoxicity, resulting in improved therapeutic efficacy in cell line and patient-derived xenograft models. Mechanistically, BLVRB signals through the transcription factor MAFB to masterfully promote the expression of various immunosuppression-associated genes, resulting in inhibitory effect against anti-AML T cells. We further demonstrated that the small molecule Tamibarotene targets BLVRB, enhancing the efficacy of both CAR-T and anti-PD-1 antibody therapies in AML. These findings elucidate the critical mechanism regulating immunosuppression in monocytic AML and identify BLVRB as a therapeutic target for improving AML immunotherapy.