Evidence mapPaperPMID 41553639Full record

ArticleCellular oncology (Dordrecht, Netherlands)2026

Aging reshapes the osteosarcoma ecosystem through immune dysfunction and tumor cell reprogramming.

Rongkai Shen, Meng Chen, Xia Zhu, Jianhua Lin

Abstract read
In one paragraph

Article in Cellular oncology (Dordrecht, Netherlands), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Rongkai ShenDepartment of Orthopedics, The First Affiliated Hospital of Fujian Medical University, 20, Chazhong Rd., Fuzhou, Fujian, 350005, China.
Meng ChenDepartment of Orthopedics, The First Affiliated Hospital of Fujian Medical University, 20, Chazhong Rd., Fuzhou, Fujian, 350005, China.
Xia ZhuDepartment of Orthopedics, The First Affiliated Hospital of Fujian Medical University, 20, Chazhong Rd., Fuzhou, Fujian, 350005, China. zhuhouy5399@fjmu.edu.cn.
Jianhua LinDepartment of Orthopedics, The First Affiliated Hospital of Fujian Medical University, 20, Chazhong Rd., Fuzhou, Fujian, 350005, China. jianhualin2025@126.com.

Funding

Fujian Provincial Finance Project BPB-2022SRKJoint Funds for the Innovation of Science and Technology, Fujian province 2021Y9095Medical Innovation Project of Fujian Provincial Health Commission 2022CXA022
6 · The paper itself

Abstract

purposeOsteosarcoma (OS) is a highly aggressive bone malignancy with particularly poor clinical outcomes in elderly patients. However, how aging reshapes the tumor immune microenvironment and tumor-intrinsic programs in OS remains largely unexplored. This study aimed to delineate age-associated remodeling of the OS tumor ecosystem and to uncover mechanisms underlying the unfavorable prognosis of elderly patients.

methodsWe performed integrated single-cell transcriptomic profiling and T cell receptor (TCR) sequencing on primary OS tumors obtained from children and young patients (CYP) and elderly individuals. Comprehensive computational analyses, including cell-type annotation, differential abundance analysis, pseudotime trajectory inference, functional enrichment, and TCR clonotype analysis, were applied to systematically characterize age-related changes across immune and malignant compartments.

resultsAging was associated with a profound reorganization of the OS immune landscape, characterized by enrichment of pro-inflammatory and pro-angiogenic macrophage subsets, accompanied by contraction of cytotoxic CD8⁺ T cells and natural killer (NK) cells and reduced TCR repertoire diversity. Pseudotime and functional analyses revealed that macrophages from elderly patients preferentially adopted terminal inflammatory and tissue-remodeling programs, whereas CYP-derived macrophages retained higher translational and metabolic activity. In parallel, tumor-intrinsic analyses uncovered age-associated transcriptional adaptations in malignant OS cells, including activation of stress-response pathways, immune evasion signatures, and dedifferentiation-related programs.

conclusionsOur study reveals coordinated aging-driven remodeling of both immune and tumor-intrinsic compartments in osteosarcoma, marked by immune dysfunction and malignant cell reprogramming. These findings provide mechanistic insight into the poor prognosis observed in elderly OS patients and suggest potential targets for age-adapted therapeutic strategies.

Indexed as

AgingBone NeoplasmsCellular ReprogrammingOsteosarcomaTumor MicroenvironmentAdolescentAdultAgedChildFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansKiller Cells, NaturalMacrophagesMaleReceptors, Antigen, T-CellAgingMyeloid reprogrammingOsteosarcomaT cell dysfunctionTumor cell adaptationTumor immune microenvironment

Identifiers

PMID41553639
PMCPMC12816095

What Socratic holds

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LicenceCC BY-NC-ND
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.