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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 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.

SUBMITTER: Ji T 

PROVIDER: S-EPMC10224931 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Integrated analysis of single-cell and bulk RNA sequencing data reveals an immunostimulatory microenvironment in tumor thrombus of osteosarcoma.

Ji Tao T   Shi Qianyu Q   Mei Song S   Xu Jiuhui J   Liang Haijie H   Xie Lu L   Ren Tingting T   Sun Kunkun K   Li Dasen D   Tang Xiaodong X   Zhang Peng P   Guo Wei W  

Oncogenesis 20230527 1


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 defin  ...[more]

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