Linbang Wang1, Tao He1, Jingkun Liu2, Jiaojiao Tai2, Bing Wang3, Zhiyu Chen1, Zhengxue Quan4. 1. Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. 2. Honghui Hospital, Xi'an Jiaotong University, 555 Youyi Dong Road, Beilin, Xi'an, 710054, Shaanxi, China. 3. Laboratory of Environmental Monitoring, Shaanxi Province Health Inspection Institution, Xi'an, 710077, Shaanxi, China. 4. Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. quanzx18@126.com.
Abstract
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.
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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