Targeting macrophage-derived SPP1 enhances CD8 T cell infiltration via ROS-DNA fragment/cGAS-STING/STAT1-mediated CXCL9/10 in tumor microenvironment

Background Elevated levels of SPP1 + tumor-associated macrophages (TAMs) are associated with reduced CD8 + T cell infiltration and poorer prognosis in cancer patients, but direct evidence demonstrating a causal role for SPP1 + TAMs in excluding CD8 + T cells is still missing. The precise mechanisms by which SPP1-activated signaling pathways and macrophage-derived factors regulate CD8 + T cell trafficking remain poorly understood. Methods We established multiple tumor mouse models to study the function of macrophage SPP1 in the tumor environment, especially its role in the relationship between macrophages and CD8 T cells. We combined the single-cell (sc) RNA sequencing data of clinical tumor samples and tumor…

• NN
  National Natural Science Foundation of China

  Awards: 82271779, 91842302, 81970457, 81901677and 91629102, 82573167