Integrated analysis of single-cell and bulk RNA sequencing data reveals an immunostimulatory microenvironment in tumor thrombus of osteosarcoma
Abstract Tumor thrombus of bone sarcomas represents a unique reservoir for various types of cancer and immune cells, however, the investigation of tumor thrombus at a single-cell level is very limited. And it is still an open question to identify the thrombus-specific tumor microenvironment that is...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-05-01
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| Series: | Oncogenesis |
| Online Access: | https://doi.org/10.1038/s41389-023-00474-2 |
| _version_ | 1797817762052046848 |
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| author | Tao Ji Qianyu Shi Song Mei Jiuhui Xu Haijie Liang Lu Xie Tingting Ren Kunkun Sun Dasen Li Xiaodong Tang Peng Zhang Wei Guo |
| author_facet | Tao Ji Qianyu Shi Song Mei Jiuhui Xu Haijie Liang Lu Xie Tingting Ren Kunkun Sun Dasen Li Xiaodong Tang Peng Zhang Wei Guo |
| author_sort | Tao Ji |
| collection | DOAJ |
| description | Abstract Tumor thrombus of bone sarcomas represents a unique reservoir for various types of cancer and immune cells, however, the investigation of tumor thrombus at a single-cell level is very limited. And it is still an open question to identify the thrombus-specific tumor microenvironment that is associated with the tumor-adaptive immune response. Here, by analyzing bulk tissue and single-cell level transcriptome from the paired thrombus and primary tumor samples of osteosarcoma (OS) patients, we define the immunostimulatory microenvironment in tumor thrombus of OS with a higher proportion of tumor-associated macrophages with M1-like states (TAM-M1) and TAM-M1 with high expression of CCL4. OS tumor thrombus is found to have upregulated IFN-γ and TGF-β signalings that are related to immune surveillance of circulating tumor cells in blood circulation. Further multiplexed immunofluorescence staining of the CD3/CD4/CD8A/CD68/CCL4 markers validates the immune-activated state in the tumor thrombus samples. Our study first reports the transcriptome differences at a single-cell level between tumor thrombus and primary tumor in sarcoma. |
| first_indexed | 2024-03-13T08:58:14Z |
| format | Article |
| id | doaj.art-3c19a883579e4b3ea0cb3b0212865e62 |
| institution | Directory Open Access Journal |
| issn | 2157-9024 |
| language | English |
| last_indexed | 2024-03-13T08:58:14Z |
| publishDate | 2023-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Oncogenesis |
| spelling | doaj.art-3c19a883579e4b3ea0cb3b0212865e622023-05-28T11:28:01ZengNature Publishing GroupOncogenesis2157-90242023-05-0112111010.1038/s41389-023-00474-2Integrated analysis of single-cell and bulk RNA sequencing data reveals an immunostimulatory microenvironment in tumor thrombus of osteosarcomaTao Ji0Qianyu Shi1Song Mei2Jiuhui Xu3Haijie Liang4Lu Xie5Tingting Ren6Kunkun Sun7Dasen Li8Xiaodong Tang9Peng Zhang10Wei Guo11Department of Musculoskeletal Tumor, People’s Hospital, Peking UniversityDepartment of Musculoskeletal Tumor, People’s Hospital, Peking UniversityShanghai Institute of Immunology, Shanghai Jiao Tong University School of MedicineDepartment of Musculoskeletal Tumor, People’s Hospital, Peking UniversityDepartment of Musculoskeletal Tumor, People’s Hospital, Peking UniversityDepartment of Musculoskeletal Tumor, People’s Hospital, Peking UniversityDepartment of Musculoskeletal Tumor, People’s Hospital, Peking UniversityDepartment of Pathology, People’s Hospital, Peking UniversityDepartment of Musculoskeletal Tumor, People’s Hospital, Peking UniversityDepartment of Musculoskeletal Tumor, People’s Hospital, Peking UniversityBeijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Rare Disease Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s HealthDepartment of Musculoskeletal Tumor, People’s Hospital, Peking UniversityAbstract Tumor thrombus of bone sarcomas represents a unique reservoir for various types of cancer and immune cells, however, the investigation of tumor thrombus at a single-cell level is very limited. And it is still an open question to identify the thrombus-specific tumor microenvironment that is associated with the tumor-adaptive immune response. Here, by analyzing bulk tissue and single-cell level transcriptome from the paired thrombus and primary tumor samples of osteosarcoma (OS) patients, we define the immunostimulatory microenvironment in tumor thrombus of OS with a higher proportion of tumor-associated macrophages with M1-like states (TAM-M1) and TAM-M1 with high expression of CCL4. OS tumor thrombus is found to have upregulated IFN-γ and TGF-β signalings that are related to immune surveillance of circulating tumor cells in blood circulation. Further multiplexed immunofluorescence staining of the CD3/CD4/CD8A/CD68/CCL4 markers validates the immune-activated state in the tumor thrombus samples. Our study first reports the transcriptome differences at a single-cell level between tumor thrombus and primary tumor in sarcoma.https://doi.org/10.1038/s41389-023-00474-2 |
| spellingShingle | Tao Ji Qianyu Shi Song Mei Jiuhui Xu Haijie Liang Lu Xie Tingting Ren Kunkun Sun Dasen Li Xiaodong Tang Peng Zhang Wei Guo Integrated analysis of single-cell and bulk RNA sequencing data reveals an immunostimulatory microenvironment in tumor thrombus of osteosarcoma Oncogenesis |
| title | Integrated analysis of single-cell and bulk RNA sequencing data reveals an immunostimulatory microenvironment in tumor thrombus of osteosarcoma |
| title_full | Integrated analysis of single-cell and bulk RNA sequencing data reveals an immunostimulatory microenvironment in tumor thrombus of osteosarcoma |
| title_fullStr | Integrated analysis of single-cell and bulk RNA sequencing data reveals an immunostimulatory microenvironment in tumor thrombus of osteosarcoma |
| title_full_unstemmed | Integrated analysis of single-cell and bulk RNA sequencing data reveals an immunostimulatory microenvironment in tumor thrombus of osteosarcoma |
| title_short | Integrated analysis of single-cell and bulk RNA sequencing data reveals an immunostimulatory microenvironment in tumor thrombus of osteosarcoma |
| title_sort | integrated analysis of single cell and bulk rna sequencing data reveals an immunostimulatory microenvironment in tumor thrombus of osteosarcoma |
| url | https://doi.org/10.1038/s41389-023-00474-2 |
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