Single-cell RNA-seq analyses inform necroptosis-associated myeloid lineages influence the immune landscape of pancreas cancer
IntroductionTumor-infiltrating myeloid cells (TIMs) are key regulators in tumor progression, but the similarity and distinction of their fundamental properties in pancreatic ductal adenocarcinoma (PDAC) remain elusive.MethodIn this study, we conducted scRNA-seq data analysis of cells from 12 primary...
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| Format: | Article |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1263633/full |
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| author | Weiwei Dong Huixia Zhao Shanshan Xiao Liuqing Zheng Tongqiang Fan Li Wang He Zhang Yanyan Hu Jingwen Yang Tao Wang Wenhua Xiao |
| author_facet | Weiwei Dong Huixia Zhao Shanshan Xiao Liuqing Zheng Tongqiang Fan Li Wang He Zhang Yanyan Hu Jingwen Yang Tao Wang Wenhua Xiao |
| author_sort | Weiwei Dong |
| collection | DOAJ |
| description | IntroductionTumor-infiltrating myeloid cells (TIMs) are key regulators in tumor progression, but the similarity and distinction of their fundamental properties in pancreatic ductal adenocarcinoma (PDAC) remain elusive.MethodIn this study, we conducted scRNA-seq data analysis of cells from 12 primary tumor (PT) tissues, 4 metastatic (Met) tumor tissues, 3 adjacent normal pancreas tissues (Para), and PBMC samples across 16 PDAC patients, and revealed a heterogeneous TIMs environment in PDAC.ResultSystematic comparisons between tumor and non-tumor samples of myeloid lineages identified 10 necroptosis-associated genes upregulated in PDAC tumors compared to 5 upregulated in paratumor or healthy peripheral blood. A novel RTM (resident tissue macrophages), GLUL-SQSTM1- RTM, was found to act as a positive regulator of immunity. Additionally, HSP90AA1+HSP90AB1+ mast cells exhibited pro-immune characteristics, and JAK3+TLR4+ CD16 monocytes were found to be anti-immune. The findings were validated through clinical outcomes and cytokines analyses. Lastly, intercellular network reconstruction supported the associations between the identified novel clusters, cancer cells, and immune cell populations.ConclusionOur analysis comprehensively characterized major myeloid cell lineages and identified three subsets of myeloid-derived cells associated with necroptosis. These findings not only provide a valuable resource for understanding the multi-dimensional characterization of the tumor microenvironment in PDAC but also offer valuable mechanistic insights that can guide the design of effective immuno-oncology treatment strategies. |
| first_indexed | 2024-03-09T00:23:46Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-09T00:23:46Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-def999620aae4a7eb2bc72567604cb112023-12-12T05:29:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-12-011410.3389/fimmu.2023.12636331263633Single-cell RNA-seq analyses inform necroptosis-associated myeloid lineages influence the immune landscape of pancreas cancerWeiwei Dong0Huixia Zhao1Shanshan Xiao2Liuqing Zheng3Tongqiang Fan4Li Wang5He Zhang6Yanyan Hu7Jingwen Yang8Tao Wang9Wenhua Xiao10Senior Dept of Oncology, The Fifth Medical Center of People's Liberation Army (PLA) General Hospital, Beijing, ChinaDept of Oncology, The Forth Medical Center of People's Liberation Army (PLA) General Hospital, Beijing, ChinaDepartment of Research and Development (R&D), Hangzhou Repugene Technology Co., Ltd., Hangzhou, ChinaDepartment of Research and Development (R&D), Hangzhou Repugene Technology Co., Ltd., Hangzhou, ChinaDepartment of Research and Development (R&D), Hangzhou Repugene Technology Co., Ltd., Hangzhou, ChinaDepartment of Research and Development (R&D), Hangzhou Repugene Technology Co., Ltd., Hangzhou, ChinaDept of Oncology, The Forth Medical Center of People's Liberation Army (PLA) General Hospital, Beijing, ChinaSenior Dept of Oncology, The Fifth Medical Center of People's Liberation Army (PLA) General Hospital, Beijing, ChinaSenior Dept of Oncology, The Fifth Medical Center of People's Liberation Army (PLA) General Hospital, Beijing, ChinaDepartment of Research and Development (R&D), Hangzhou Repugene Technology Co., Ltd., Hangzhou, ChinaSenior Dept of Oncology, The Fifth Medical Center of People's Liberation Army (PLA) General Hospital, Beijing, ChinaIntroductionTumor-infiltrating myeloid cells (TIMs) are key regulators in tumor progression, but the similarity and distinction of their fundamental properties in pancreatic ductal adenocarcinoma (PDAC) remain elusive.MethodIn this study, we conducted scRNA-seq data analysis of cells from 12 primary tumor (PT) tissues, 4 metastatic (Met) tumor tissues, 3 adjacent normal pancreas tissues (Para), and PBMC samples across 16 PDAC patients, and revealed a heterogeneous TIMs environment in PDAC.ResultSystematic comparisons between tumor and non-tumor samples of myeloid lineages identified 10 necroptosis-associated genes upregulated in PDAC tumors compared to 5 upregulated in paratumor or healthy peripheral blood. A novel RTM (resident tissue macrophages), GLUL-SQSTM1- RTM, was found to act as a positive regulator of immunity. Additionally, HSP90AA1+HSP90AB1+ mast cells exhibited pro-immune characteristics, and JAK3+TLR4+ CD16 monocytes were found to be anti-immune. The findings were validated through clinical outcomes and cytokines analyses. Lastly, intercellular network reconstruction supported the associations between the identified novel clusters, cancer cells, and immune cell populations.ConclusionOur analysis comprehensively characterized major myeloid cell lineages and identified three subsets of myeloid-derived cells associated with necroptosis. These findings not only provide a valuable resource for understanding the multi-dimensional characterization of the tumor microenvironment in PDAC but also offer valuable mechanistic insights that can guide the design of effective immuno-oncology treatment strategies.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1263633/fullscRNA-seqPDACTIMsnecroptosisTME |
| spellingShingle | Weiwei Dong Huixia Zhao Shanshan Xiao Liuqing Zheng Tongqiang Fan Li Wang He Zhang Yanyan Hu Jingwen Yang Tao Wang Wenhua Xiao Single-cell RNA-seq analyses inform necroptosis-associated myeloid lineages influence the immune landscape of pancreas cancer Frontiers in Immunology scRNA-seq PDAC TIMs necroptosis TME |
| title | Single-cell RNA-seq analyses inform necroptosis-associated myeloid lineages influence the immune landscape of pancreas cancer |
| title_full | Single-cell RNA-seq analyses inform necroptosis-associated myeloid lineages influence the immune landscape of pancreas cancer |
| title_fullStr | Single-cell RNA-seq analyses inform necroptosis-associated myeloid lineages influence the immune landscape of pancreas cancer |
| title_full_unstemmed | Single-cell RNA-seq analyses inform necroptosis-associated myeloid lineages influence the immune landscape of pancreas cancer |
| title_short | Single-cell RNA-seq analyses inform necroptosis-associated myeloid lineages influence the immune landscape of pancreas cancer |
| title_sort | single cell rna seq analyses inform necroptosis associated myeloid lineages influence the immune landscape of pancreas cancer |
| topic | scRNA-seq PDAC TIMs necroptosis TME |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1263633/full |
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