Interaction gene set between osteoclasts and regulatory CD4+ T cells can accurately predict the prognosis of patients with osteosarcoma
Open accessAbstract
Osteoclasts (OCs) and regulatory CD4+ T cells (CD4+Tregs) are important components in the tumor microenvironment (TME) of osteosarcoma. In this study, we collected six osteosarcoma samples from our previous study (GSE162454). We also integrated a public database (GSE152048), which included single cell sequencing data of 11 osteosarcoma patients. We obtained 138,192 cells and then successfully identified OCs and CD4+Tregs. Based on the interaction gene set between OCs and CD4+Tregs, patients from GSE21257 were distinguished into two clusters by consensus clustering analysis. Both the tumor immune microenvironment and survival prognosis between the two clusters were significantly different. Subsequently, five model genes were identified by protein–protein interaction network based on differentially upregulated genes of cluster 2. Quantitative RT‐PCR was used to detect their expression in human osteoblast and osteosarcoma cells. A prognostic model was successfully established using these five genes. Kaplan–Meier survival analysis found that patients in the high‐risk group had worse survival (p = 0.029). Therefore, our study first found that cell–cell communication between OCs and CD4+Tregs significantly alters TME and is connected to poor prognosis of OS. The model we constructed can accurately predict prognosis for osteosarcoma patients.
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Treg cells secrete immunosuppressive cytokines such as IL-10, IL-35, and TGF-β to inhibit the activity of effector T cells, and inhibit the formation of osteoclasts through direct cell contact-dependent manners.
“They secrete immunosuppressive cytokines such as IL-10, IL-35, and TGF-β to inhibit the activity of effector T cells, and inhibit the formation of osteoclasts through direct cell contact-dependent manners [34].”
From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [34]
The Discussion (page unavailable) says CD4+ regulatory T cells contribute to immunosuppression by secreting cytokines. It does not identify IL-10, IL-35, or TGF-β as cytokines secreted by those cells, or say that they inhibit osteoclast formation through direct cell contact; its mention of IL-10 concerns osteoclasts. (LLM, conf=0.86)
Experimental — accuracy not yet measuredInteraction of CD4+ Tregs and osteoclasts significantly alters TME and is connected to poor prognosis of osteosarcoma.
“Interaction of CD4+ Tregs and osteoclasts significantly alters TME and is connected to poor prognosis of osteosarcoma [34].”
From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [34]
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Cites
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Meltzer, P. S., & Helman, L. J. (2021) · New England Journal of Medicine · doi:10.1056/nejmra2103423 · Cited by 672 · see citing works
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Advances on immunotherapy for osteosarcoma
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- Authors
- Li, F., Tang, H., Luo, X., Li, X., Luo, K., Liu, S., Liang, J., Liao, S., Zhong, C., Zhan, X., Wei, Q., Feng, W., & Liu, Y.
- Affiliations
- Guangxi Medical University (CN)
- First Affiliated Hospital of GuangXi Medical University (CN)
- Corresponding author
- Feng, Wenyu
- Liu, Yun
- ORCID
- Venue
- Cancer Science
- Publisher
- Wiley
- Published
- 2023-05-07
- Volume
- 114
- Issue
- 7
- Pages
- 3014-3026
- ISSN
- 1347-9032 (ISSN-L)
- 1349-7006
- PMC
- PMC10323104
- OpenAlex
- W4375855833
- Cited by
- 22
- References
- 5
- Citations by year
- 2026: 2 · 2025: 11 · 2024: 7 · 2023: 2
- FWCI
- 4.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancer Science (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81960768, 82260814)
- Natural Science Foundation of Guangxi Province (2020GXNSFAA259088)
- Youth Science Foundation of Guangxi Medical University (GXMUYSF202129, GXMUYSF202313)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
- Keywords
- osteosarcoma, osteoclasts, CD4+ regulatory T cells, tumor microenvironment, intercellular communication, prognostic gene signature, survival prediction, protein-protein interaction network, single-cell RNA sequencing, consensus clustering
- MeSH terms
- Bone Neoplasms, Humans, Osteoclasts, Prognosis, Osteosarcoma, T-Lymphocytes, CD4-Positive T-Lymphocytes, Tumor Microenvironment
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