SPP1þmacrophages in colorectal cancer:Markers of malignancy and promising therapeutic targets  

作　　者：Zhenyu Xie Gaozan Zheng Liaoran Niu Kunli Du Ruikai Li Hanjun Dan Lili Duan Hongze Wu Guangming Ren Xinyu Dou Songchen Dai Fan Feng Jian Zhang Jianyong Zheng 

机构地区：[1]Department of Digestive Surgery,Xijing Hospital of Digestive Diseases,Medical University,Xi’an,Shaanxi 710032,China [2]Xi’an Medical University,Xi’an,Shaanxi 710021,China [3]Department of Surgical Oncology and General Surgery,The First Hospital of China Medical University,Shenyang,Liaoning 110016,China [4]Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors,Ministry of Education,Shenyang,Liaoning 110016,China [5]The State Key Laboratory of Cancer Biology,Department of Biochemistry and Molecular Biology,Air Force Medical University,Xi’an,Shaanxi 710032,China

出　　处：《Genes & Diseases》2025年第3期428-446,共19页基因与疾病(英文)

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).

摘　　要：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.

关 键 词：Colorectal cancer Immunotherapy Single-cell RNA sequencing Spatial transcriptomics SPP1þmacrophages 

分 类 号：R73[医药卫生—肿瘤]