Single-cell Atlas Reveals Myelopoietic Bias and Immunosuppressive Reprogramming in Metastatic Bone Marrow Across...

Bone metastasis can remodel the bone marrow microenvironment, yet how metastatic tumors reshape hematopoiesis and immunity across marrow regions remains poorly defined. Here, we profile a cross-cancer single-cell atlas with 126,986 cells by integrating bone marrow samples (tumor, involved, and distal sites) from liver, prostate, and kidney cancer bone metastases, as well as benign controls, resolving 7 major lineages and 66 subpopulations. We identified coordinated immune suppression and niche remodeling that innate cells rose in peri-tumoral marrow but dropped in tumor sites, while adaptive T/B cells progressively depleted and stromal/epithelial compartments expanded. We further revealed a shift in myelopoiesis toward immunosuppressive monocyte/macrophage states with GMP-level lineage bias, alongside impaired erythropoiesis and B lymphopoiesis driven by myeloid-like reprogramming of precursors. Tumor sites were enriched with exhausted/stressed T cells, linked to inhibitory progenitor-T cell interactions (e.g., LGALS9-HAVCR2 and CLEC2-KLRB1). Non-hematopoietic support signals (CXCL12-CXCR4, ICAM1-SPN) were attenuated, and tumor programs included a marrow-specific metaprogram with IGFBP3/NAMPT signaling predicted to further destabilize the HSC niche. Overall, our study offers an integrated framework for decoding the metastatic marrow ecosystem by jointly targeting hematopoietic distortion, stromal collapse, and immune dysfunction.