趋化因子定义的巨噬细胞生态位建立肿瘤免疫的空间组织

Macrophages are among the most abundant immune cells in solid tumors, yet how macrophage lineage and spatial organization shape antitumor immunity remains unclear. Here we uncovered a division of labor between tissue-resident CD206hi and CD206lo interstitial macrophage (IM) subsets and Ly6c2+Fn1+Vcan+ recruited macrophages (recMacs) in lung cancer. Using single-cell and spatial transcriptomics, we identified chemokine-expressing IM subsets with opposing functions. Cxcl13+CD206hi IMs, Cxcl9+CD206hi IMs and Cxcl10+CD206hi IMs positioned along bronchovascular regions drove tertiary lymphoid structure formation, lymphocyte recruitment and tumor control, whereas Ccl2+ IMs, localized within tumor regions, recruited protumorigenic Ly6c2+Fn1+Vcan+ recMacs. In addition, Ly6C+CD11b+ monocyte-derived dendritic cells (moDCs) functioned as immunosuppressive antigen-presenting cells in tumor-draining lymph nodes. During neoantigen vaccination, CCR5 blockade with maraviroc selectively inhibited antigen-bearing moDC migration, enhancing dendritic cell-mediated antitumor immunity. These findings showed how macrophage lineage and spatial compartmentalization govern tumor immunity and identified strategies to preserve protective IM functions, while disrupting macrophage-driven immunosuppression.