Evidence map›Paper›PMID 42178443›Full record

ArticleApoptosis : an international journal on programmed cell death2026

Osteopontin-driven TGF-β1 signaling via integrin αvβ3-NF-κB axis impairs NK cell function in head and neck squamous cell carcinoma.

Zhe Shen, Xin Li, Shi Luo, Yuzhang Gao, Imadoudini Hassimi Safia, Jie Jiang, Xin Qi, Wei Huang, Yalan Liu, Xing Fang and 2 more

Abstract read
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In one paragraph

Article in Apoptosis : an international journal on programmed cell death, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Zhe Shen *Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.
Xin Li *Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.
Shi LuoThe Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, Hunan, China.
Yuzhang GaoDepartment of Medicine (Cardiology, Angiology), Heidelberg University, Mannheim, Germany.
Imadoudini Hassimi SafiaDepartment of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.
Jie JiangDepartment of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.
Xin QiDepartment of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.
Wei HuangResearch Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, China.
Yalan LiuDepartment of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.
Xing FangDepartment of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.
Yaoyun TangDepartment of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.
Ping WuDepartment of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China. wuping419@csu.edu.cn.

Funding

the Central South University Graduate Research Innovation Project No. 1053320232374the Hunan Provincial Natural Science Foundation No. 2023JJ30945
6 · The paper itself

Abstract

In head and neck squamous cell carcinoma (HNSCC), an immunosuppressive tumor microenvironment (TME) frequently leads to natural killer (NK) cell dysfunction, but the molecular mechanisms underlying this impairment remain unclear. Here, we combined flow cytometry and multiplex immunohistochemistry to evaluate NK cells infiltration and functional status in HNSCC tumors. Bulk RNA-seq datasets from patient cohorts and single-cell RNA-seq data were analyzed to identify transcriptional correlates of NK cells dysfunction. Mechanistic studies in tumor cell lines assessed the role of osteopontin (OPN)-integrin αvβ3/NF-κB signaling in modulating TGF-β1 production and its effects on NK cell activity. NK cells in HNSCC tumors exhibited reduced infiltration and diminished activation marker expression, coinciding with high OPN levels in the TME. Transcriptomic analyses demonstrated a strong inverse correlation between tumor SPP1 (encoding OPN) expression and NK cells abundance. Mechanistically, tumor-derived OPN engaged integrin αvβ3 to activate NF-κB signaling, inducing robust TGF-β1 secretion that suppressed NK cell activation and cytotoxic function. Single-cell RNA-seq analysis further confirmed the exhausted functional states of NK cells within the HNSCC TME. Tumor-derived OPN promotes immune evasion in HNSCC by driving TGF-β1-mediated suppression of NK cell activity. These findings highlight the OPN-TGF-β1 axis as a potential therapeutic target for restoring NK cell-mediated immunity in HNSCC.

Indexed as

Head and Neck NeoplasmsIntegrin alphaVbeta3Killer Cells, NaturalNF-kappa BOsteopontinSquamous Cell Carcinoma of Head and NeckTransforming Growth Factor beta1AnimalsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansSignal TransductionTumor MicroenvironmentIntegrin alphaVbeta3NF-kappa BOsteopontinSPP1 protein, humanTGFB1 protein, humanTransforming Growth Factor beta1Head and neck squamous cell carcinomaNK cellsOsteopontinTGF-β1Tumor microenvironment

Identifiers

PMID42178443

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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 OpenQuestion graph.