Pan-cancer analysis reveals tumor-associated macrophage communication in the tumor microenvironment

Background Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment (TME). However, their contribution to the immunosuppressive status of the TME remains unclear. Methods We integrated single-cell sequencing and transcriptome data from different tumor types to uncover the molec...

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Veröffentlicht in:Experimental hematology & oncology Jg. 10; H. 1; S. 31 - 19
Hauptverfasser: Wang, Linbang, He, Tao, Liu, Jingkun, Tai, Jiaojiao, Wang, Bing, Chen, Zhiyu, Quan, Zhengxue
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London BioMed Central 10.05.2021
BioMed Central Ltd
Springer Nature B.V
BMC
Schlagworte:
Analysis
Cancer
Cancer Research
Communication
Cytokines
Development and progression
FLI1
Gene expression
Genotype & phenotype
Hematology
Immunotherapy
Intercellular communication
Ligands
Macrophages
Medical prognosis
Medicine
Medicine & Public Health
Melanoma
Oncology
Principal components analysis
Tumor microenvironment
Tumor-associated macrophages
Tumors
China
Tumor microenvironment
Tumor-associated macrophages
Intercellular communication
FLI1
ISSN:2162-3619, 2162-3619
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Zusammenfassung:Background Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment (TME). However, their contribution to the immunosuppressive status of the TME remains unclear. Methods We integrated single-cell sequencing and transcriptome data from different tumor types to uncover the molecular features of TAMs. In vitro experiments and prospective clinical tests confirmed the results of these analysis. Results We first detected intra- and inter-tumoral heterogeneities between TAM subpopulations and their functions, with CD86 + TAMs playing a crucial role in tumor progression. Next, we focused on the ligand-receptor interactions between TAMs and tumor cells in different TME phenotypes and discovered that aberrant expressions of six hub genes, including FLI1 , are involved in this process. A TAM-tumor cell co-culture experiment proved that FLI1 was involved in tumor cell invasion, and FLI1 also showed a unique pattern in patients. Finally, TAMs were discovered to communicate with immune and stromal cells. Conclusion We determined the role of TAMs in the TME by focusing on their communication pattern with other TME components. Additionally, the screening of hub genes revealed potential therapeutic targets.
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ISSN:2162-3619
2162-3619
DOI:10.1186/s40164-021-00226-1