Evidence mapPaperPMID 42507293Full record

ArticleMolecular biology reports2026

Tumor-derived ITGB3 shapes a primed but functionally constrained NK cell state in breast cancer through HLA-E-NKG2A signaling.

Kunqin Wang, Xinyue Bao, Jun Yan, Jiarui Xu, Chenghan Ju, Ruijie Cao, Qi Sun

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Article in Molecular biology reports, 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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5 · Who and what money

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7 authors.

Kunqin Wang *Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Xinyue Bao *Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Jun Yan *Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Jiarui XuDepartment of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Chenghan JuDepartment of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Ruijie CaoDepartment of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Qi SunDepartment of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China. sunqi4875@163.com.

Funding

Fundamental Research Funds of Xi'an Jiaotong University xzy012023108Key Science and Technology Program of Shaanxi Province 2025SF-YBXM-220National Natural Science Foundation of China 82473053
6 · The paper itself

Abstract

backgroundNatural killer (NK) cells are vital for anti-tumor immunity, yet their effector functions are frequently constrained within the tumor microenvironment. Integrin β3 (ITGB3) has been implicated in breast cancer progression and stemness, but whether ITGB3 expression in malignant cells influences NK cell states and contributes to immune evasion remains unclear.

methodsSingle-cell RNA sequencing data were utilized to profile the transcriptomic and metabolic divergence of NK cells between ITGB3⁺ and ITGB3⁻ tumor microenvironments. Cell-cell communication and pseudotime trajectory analyses were performed to identify key signaling axes. The SCIPAC framework was employed to map single-cell subsets to the bulk TCGA-BRCA cohort for clinical correlation. The mechanistic findings were validated through in vitro co-culture assays and NKG2A blocking experiments using MDA-MB-231 and BT-474 cell lines.

resultsNK cells associated with ITGB3

conclusionsITGB3 expression in malignant cells is associated with a primed but functionally constrained NK cell state in breast cancer. Increased malignant-cell HLA-E expression and restoration of IFN-γ production following NKG2A blockade support a functional contribution of the inhibitory NKG2A branch, without excluding concurrent activating signaling through NKG2C.

Indexed as

Breast NeoplasmsHistocompatibility Antigens Class IIntegrin beta3Killer Cells, NaturalNK Cell Lectin-Like Receptor Subfamily CCell CommunicationCell Line, TumorFemaleGene Expression Regulation, NeoplasticHLA-E AntigensHumansMDA-MB-231 CellsSignal TransductionTumor MicroenvironmentHistocompatibility Antigens Class IHLA-E AntigensIntegrin beta3ITGB3 protein, humanKLRC1 protein, humanNK Cell Lectin-Like Receptor Subfamily CBreast cancerHLA-EIntegrin β3Natural killer cellNKG2ASingle-cell analysis

Identifiers

PMID42507293

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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.