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已发表论文
利用单细胞和空间转录组测序解码胶质母细胞瘤中与预后相关的 S100A9 高表达单核细胞
Authors Li X, Qin Y, Gao P, Wang H, Liu Y, Ren L, Wu D, Heng X
Received 11 July 2025
Accepted for publication 24 October 2025
Published 5 November 2025 Volume 2025:18 Pages 1211—1226
DOI https://doi.org/10.2147/OTT.S553018
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr John Riches
Xiucan Li,1,2 Ying Qin,3 Pengfei Gao,2 Huixue Wang,2 Yanling Liu,4 Lian Ren,5 Dongdong Wu,6 Xueyuan Heng2
1Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Orthopedics, Linyi People’s Hospital, Linyi, Shandong Province, People’s Republic of China; 3Department of Gastroenterology, Hospital of Traditional Chinese Medicine of Linyi City, Linyi, Shandong Province, People’s Republic of China; 4Department of General Medicine, Linyi People’s Hospital, Linyi, Shandong Province, People’s Republic of China; 5Graduate School, Dalian Medical University, Dalian, Liaoning Province, People’s Republic of China; 6Chinese PLA General Hospital, Beijing, People’s Republic of China
Correspondence: Xueyuan Heng, Department of Orthopedics, Linyi People’s Hospital, Linyi, Shandong Province, People’s Republic of China, Tel +86-13608990919, Email hengxueyuan123@126.com
Purpose: Monocytes and macrophages are recognized as predominant immune populations in human glioblastoma, where they play vital roles in tumor progression. Despite their established significance, the heterogeneity of these cells—particularly within the monocyte compartment—remains incompletely characterized.
Methods: We comprehensively used scRNA-seq, spatial transcriptome sequencing combined with immunofluorescence and T cell co-culture assays to illuminate the heterogeneity and function of monocyte in glioblastoma.
Results: In this study, from the perspective of ligand-receptor networks, we have identified and characterized three distinct glioblastoma subtypes. Single-cell RNA-seq analysis further revealed that the C3 subtype with bad prognosis exhibited a higher proportion of S100A9high monocytes. Spatial transcriptomics combined with immunofluorescence assays demonstrated that these S100A9high monocytes were spatially adjacent to M2 macrophages, exhausted CD8+ T cells, and endothelial cells. In vitro T cell co-culture assays revealed S100A9high monocyte produced elevated levels of the immunosuppressive cytokine IL-10, reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS), all of which might impair T cell function and immune response. Notably, elevated abundance of S100A9high monocyte correlated with poor patient prognosis.
Conclusion: In summary, our results deciphered the heterogeneity of monocytes in glioblastoma and identified a novel poor prognosis-associated monocyte subset, S100A9high monocytes, which foster an immunosuppressive, pro-tumorigenic microenvironment.
Keywords: tumor associated monocyte, glioblastoma, immune environment, scRNA-seq, spatial transcriptome sequencing
1Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Orthopedics, Linyi People’s Hospital, Linyi, Shandong Province, People’s Republic of China; 3Department of Gastroenterology, Hospital of Traditional Chinese Medicine of Linyi City, Linyi, Shandong Province, People’s Republic of China; 4Department of General Medicine, Linyi People’s Hospital, Linyi, Shandong Province, People’s Republic of China; 5Graduate School, Dalian Medical University, Dalian, Liaoning Province, People’s Republic of China; 6Chinese PLA General Hospital, Beijing, People’s Republic of China
Correspondence: Xueyuan Heng, Department of Orthopedics, Linyi People’s Hospital, Linyi, Shandong Province, People’s Republic of China, Tel +86-13608990919, Email hengxueyuan123@126.com
Purpose: Monocytes and macrophages are recognized as predominant immune populations in human glioblastoma, where they play vital roles in tumor progression. Despite their established significance, the heterogeneity of these cells—particularly within the monocyte compartment—remains incompletely characterized.
Methods: We comprehensively used scRNA-seq, spatial transcriptome sequencing combined with immunofluorescence and T cell co-culture assays to illuminate the heterogeneity and function of monocyte in glioblastoma.
Results: In this study, from the perspective of ligand-receptor networks, we have identified and characterized three distinct glioblastoma subtypes. Single-cell RNA-seq analysis further revealed that the C3 subtype with bad prognosis exhibited a higher proportion of S100A9high monocytes. Spatial transcriptomics combined with immunofluorescence assays demonstrated that these S100A9high monocytes were spatially adjacent to M2 macrophages, exhausted CD8+ T cells, and endothelial cells. In vitro T cell co-culture assays revealed S100A9high monocyte produced elevated levels of the immunosuppressive cytokine IL-10, reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS), all of which might impair T cell function and immune response. Notably, elevated abundance of S100A9high monocyte correlated with poor patient prognosis.
Conclusion: In summary, our results deciphered the heterogeneity of monocytes in glioblastoma and identified a novel poor prognosis-associated monocyte subset, S100A9high monocytes, which foster an immunosuppressive, pro-tumorigenic microenvironment.
Keywords: tumor associated monocyte, glioblastoma, immune environment, scRNA-seq, spatial transcriptome sequencing