SPP1^(+) macrophages have been identified as key players in the colorectal cancer(CRC) tumor microenvironment, but their function remains unclear. This study integrated single-cell and spatial transcriptomics with bul...SPP1^(+) macrophages have been identified as key players in the colorectal cancer(CRC) tumor microenvironment, but their function remains unclear. This study integrated single-cell and spatial transcriptomics with bulk sequencing to investigate the roles and mechanisms of SPP1^(+) macrophages in CRC. Our findings revealed a pronounced elevation of SPP1^(+)macrophages in CRC, especially within tumor territories. These macrophages served asmarkers for CRC initiation, progression, metastasis, and potential prognosis. Furthermore,they showed heightened transcriptional activity in genes linked to angiogenesis, epithelialemesenchymal transition, glycolysis, hypoxia, and immunosuppression. SPP1 protein amplifiedCRC cell migration and invasion, potentially mediating cellular crosstalk via the SPP1-CD44,SPP1-PTGER4, and SPP1-a4b1 complex axes. Patients with a high proportion of SPP1^(+) macrophages could benefit more from immune checkpoint blockade therapy. Interestingly, CSF1R expression was significantly enriched in C1QC^(+) macrophages versus SPP1^(+) macrophages,possibly explaining limited anti-CSF1R monotherapy effects. In conclusion, we propose anSPP1^(+) macrophage model in CRC, highlighting such macrophages as a promising therapeutictarget due to their malignancy markers.展开更多
基金supported by the National Natural Science Foundation of China(No.82072655)the Scientific and technological innovation team of Shaanxi Innovation Capability Support Plan(China)(No.2023-CX-TD-67)the Key R&D Plan of Shaanxi Province,China(No.2022SF-603).
文摘SPP1^(+) macrophages have been identified as key players in the colorectal cancer(CRC) tumor microenvironment, but their function remains unclear. This study integrated single-cell and spatial transcriptomics with bulk sequencing to investigate the roles and mechanisms of SPP1^(+) macrophages in CRC. Our findings revealed a pronounced elevation of SPP1^(+)macrophages in CRC, especially within tumor territories. These macrophages served asmarkers for CRC initiation, progression, metastasis, and potential prognosis. Furthermore,they showed heightened transcriptional activity in genes linked to angiogenesis, epithelialemesenchymal transition, glycolysis, hypoxia, and immunosuppression. SPP1 protein amplifiedCRC cell migration and invasion, potentially mediating cellular crosstalk via the SPP1-CD44,SPP1-PTGER4, and SPP1-a4b1 complex axes. Patients with a high proportion of SPP1^(+) macrophages could benefit more from immune checkpoint blockade therapy. Interestingly, CSF1R expression was significantly enriched in C1QC^(+) macrophages versus SPP1^(+) macrophages,possibly explaining limited anti-CSF1R monotherapy effects. In conclusion, we propose anSPP1^(+) macrophage model in CRC, highlighting such macrophages as a promising therapeutictarget due to their malignancy markers.
