Single-cell transcriptome analysis identifies a novel tumor-associated macrophage subtype predicting better prognosis in pancreatic ductal adenocarcinoma
BackgroundCharacterized by an immune-suppressive tumor microenvironment (TME), pancreatic ductal adenocarcinoma (PDAC) is well-known for its poor prognosis. Tumor associated macrophages (TAMs) play a critical role in PDAC TME. An in-depth understanding of TAMs is helpful to develop new strategies fo...
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Frontiers Media S.A.
2024-10-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2024.1466767/full |
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| author | Xiaonan Wang Dongyi Li Bo Zhu Zichun Hua Zichun Hua Zichun Hua Zichun Hua |
| author_facet | Xiaonan Wang Dongyi Li Bo Zhu Zichun Hua Zichun Hua Zichun Hua Zichun Hua |
| author_sort | Xiaonan Wang |
| collection | DOAJ |
| description | BackgroundCharacterized by an immune-suppressive tumor microenvironment (TME), pancreatic ductal adenocarcinoma (PDAC) is well-known for its poor prognosis. Tumor associated macrophages (TAMs) play a critical role in PDAC TME. An in-depth understanding of TAMs is helpful to develop new strategies for immunotherapy.MethodsA large number of single-cell RNA sequencing data and bulk RNA sequencing data of PDAC were collected for systematic bioinformatics analysis. Characterize subtypes of TAMs at single-cell resolution and its effect on prognosis. Differential gene analysis and cell-cell communication were used to describe the effect on prognosis and validated by the TCGA dataset.ResultsWe used two prognosis-favorable genes, SLC12A5 and ENPP2, to identify a benign M2-like TAMs (bM2-like TAMs), which shared similarities with C1QC + TAMs, CXCL9+ TAMs and CD169+ TAMs, by analyzing scRNA-seq data and bulk RNA data of PDAC. The bM2-like TAMs were revealed to promote T cell activation and proliferation through ALCAM/CD6 interaction. Meanwhile, the bM2-like TAMs were responsible for stroma modeling by altering αSMA+/αSMA-cell ratio. On the contrast, the rest of the M2-like TAMs were defined as malignant M2-like TAMs (mM2-like TAMs), partly overlapping with SPP1+ TAMs. mM2-like TAMs were revealed to promote tumor progression by secretion of MIF and SPP1.ConclusionOur study used two prognosis-favorable genes to divide M2-like TAMs of PDAC into anti-tumor bM2-like TAMs and pro-tumor mM2-like TAMs. The bM2-like TAMs activate T cells through ALCAM/CD6 and generate prognosis-favorable αSMA+ myofibroblasts through secreting TGFβ, which brings insight into heterogeneity of TAMs, prognosis prediction and immunotherapy of PDAC. |
| format | Article |
| id | doaj-art-e069c82a8b3c4e9abbf5f477fc9966f4 |
| institution | OA Journals |
| issn | 2296-634X |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-e069c82a8b3c4e9abbf5f477fc9966f42025-08-20T02:09:47ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2024-10-011210.3389/fcell.2024.14667671466767Single-cell transcriptome analysis identifies a novel tumor-associated macrophage subtype predicting better prognosis in pancreatic ductal adenocarcinomaXiaonan Wang0Dongyi Li1Bo Zhu2Zichun Hua3Zichun Hua4Zichun Hua5Zichun Hua6School of Biopharmacy, China Pharmaceutical University, Nanjing, ChinaSchool of Biopharmacy, China Pharmaceutical University, Nanjing, ChinaSchool of Biopharmacy, China Pharmaceutical University, Nanjing, ChinaSchool of Biopharmacy, China Pharmaceutical University, Nanjing, ChinaThe State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, ChinaFaculty of Pharmaceutical Sciences, Xinxiang Medical University, Xinxiang, ChinaChangzhou High-Tech Research Institute, Nanjing University, Changzhou, ChinaBackgroundCharacterized by an immune-suppressive tumor microenvironment (TME), pancreatic ductal adenocarcinoma (PDAC) is well-known for its poor prognosis. Tumor associated macrophages (TAMs) play a critical role in PDAC TME. An in-depth understanding of TAMs is helpful to develop new strategies for immunotherapy.MethodsA large number of single-cell RNA sequencing data and bulk RNA sequencing data of PDAC were collected for systematic bioinformatics analysis. Characterize subtypes of TAMs at single-cell resolution and its effect on prognosis. Differential gene analysis and cell-cell communication were used to describe the effect on prognosis and validated by the TCGA dataset.ResultsWe used two prognosis-favorable genes, SLC12A5 and ENPP2, to identify a benign M2-like TAMs (bM2-like TAMs), which shared similarities with C1QC + TAMs, CXCL9+ TAMs and CD169+ TAMs, by analyzing scRNA-seq data and bulk RNA data of PDAC. The bM2-like TAMs were revealed to promote T cell activation and proliferation through ALCAM/CD6 interaction. Meanwhile, the bM2-like TAMs were responsible for stroma modeling by altering αSMA+/αSMA-cell ratio. On the contrast, the rest of the M2-like TAMs were defined as malignant M2-like TAMs (mM2-like TAMs), partly overlapping with SPP1+ TAMs. mM2-like TAMs were revealed to promote tumor progression by secretion of MIF and SPP1.ConclusionOur study used two prognosis-favorable genes to divide M2-like TAMs of PDAC into anti-tumor bM2-like TAMs and pro-tumor mM2-like TAMs. The bM2-like TAMs activate T cells through ALCAM/CD6 and generate prognosis-favorable αSMA+ myofibroblasts through secreting TGFβ, which brings insight into heterogeneity of TAMs, prognosis prediction and immunotherapy of PDAC.https://www.frontiersin.org/articles/10.3389/fcell.2024.1466767/fullsingle-cell sequencingpancreatic cancertumor associated macrophagestumor microenvironmentprognosis |
| spellingShingle | Xiaonan Wang Dongyi Li Bo Zhu Zichun Hua Zichun Hua Zichun Hua Zichun Hua Single-cell transcriptome analysis identifies a novel tumor-associated macrophage subtype predicting better prognosis in pancreatic ductal adenocarcinoma Frontiers in Cell and Developmental Biology single-cell sequencing pancreatic cancer tumor associated macrophages tumor microenvironment prognosis |
| title | Single-cell transcriptome analysis identifies a novel tumor-associated macrophage subtype predicting better prognosis in pancreatic ductal adenocarcinoma |
| title_full | Single-cell transcriptome analysis identifies a novel tumor-associated macrophage subtype predicting better prognosis in pancreatic ductal adenocarcinoma |
| title_fullStr | Single-cell transcriptome analysis identifies a novel tumor-associated macrophage subtype predicting better prognosis in pancreatic ductal adenocarcinoma |
| title_full_unstemmed | Single-cell transcriptome analysis identifies a novel tumor-associated macrophage subtype predicting better prognosis in pancreatic ductal adenocarcinoma |
| title_short | Single-cell transcriptome analysis identifies a novel tumor-associated macrophage subtype predicting better prognosis in pancreatic ductal adenocarcinoma |
| title_sort | single cell transcriptome analysis identifies a novel tumor associated macrophage subtype predicting better prognosis in pancreatic ductal adenocarcinoma |
| topic | single-cell sequencing pancreatic cancer tumor associated macrophages tumor microenvironment prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2024.1466767/full |
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