Evidence map›Paper›PMID 42407378›Full record

ArticleTranslational oncology2026

Entosis remodels the immune microenvironment of osteosarcoma by regulating macrophage polarization: An integrated study based on multi-omics data and in vitro experiments.

Guoling Huang, Yongbo Xiao, Hongliang Zhang, Yu Liu

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Article in Translational oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Guoling HuangDepartment of Pathology, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China.
Yongbo XiaoHunan University of Medicine, Huaihua, Hunan, 418000, China.
Hongliang ZhangDepartment of Orthopaedics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China. Electronic address: HB2H@126.com.
Yu LiuSchool of Basic Medicine Science, Hunan University of Medicine, Huaihua, Hunan, 418000, China. Electronic address: Noah1604@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEntosis is a non-apoptotic form of programmed cell death. Its clinical significance and mechanism of immune microenvironment remodeling in osteosarcoma remain poorly understood.

methodsMulti-omics data from TARGET-OS and GEO were integrated with in vitro experiments. ssGSEA, WGCNA, scRNA-seq, pseudotime analysis, and cell-cell communication were used to assess Entosis activity and immune association. A prognostic risk model was constructed and validated. In vitro experiments (qPCR, flow cytometry, Western blot, ELISA) validated Entosis regulation of macrophage polarization.

resultsHigh Entosis activity was significantly correlated with favorable prognosis and a highly activated immune microenvironment in osteosarcoma patients. scRNA-seq identified macrophages as the core target cells of Entosis regulation, and the Macro_CXCL2 subset was characterized as the functional subpopulation with the highest Entosis score at the terminal differentiation stage. Cell communication analysis revealed that, under high Entosis conditions, macrophages enhanced crosstalk with other immune cells via the SPP1-CD44 and TNF signaling axes. A six-gene prognostic model (CD163, FCGR2A, NPC2, CD209, SAMHD1, IKZF1) demonstrated robust performance across multiple datasets. In vitro experiments further confirmed that high-Entosis tumor cells upregulated CXCL12 secretion in a paracrine manner, driving macrophages toward a specific functional phenotype. Mechanistically, Entosis activation was dependent on the ROCK signaling pathway and synergized with the hypoxia, TNFα-NFκB, and MAPK pathways to coordinately regulate malignant cell stemness and immune microenvironment remodeling.

conclusionEntosis exerts tumor-suppressive and immune-activating effects in osteosarcoma by remodeling macrophage function, offering new targets for precision prognosis and Entosis-directed immunotherapy.

Indexed as

CXCL12EntosisMacrophage polarizationOsteosarcomaPrognostic model

Identifiers

PMID42407378
PMCPMC13355408

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