Evidence map›Paper›PMID 41280896›Full record

ArticleFrontiers in immunology2025

NK cell function down regulated by HMGB2 through ANGPT1/PI3K/AKT pathway and its effect on esophageal squamous carcinoma cells.

Xiaodi Yin, Huihong Cai, Aohua Zhang, Weihan Zheng, Jiahui Zhao, Jun Ma

Abstract read
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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

The trial behind it

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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

1 citing paper in PubMed.

  1. Article
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

6 authors.

Xiaodi Yin *Department of Clinical Laboratory, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Huihong Cai *Department of Clinical Laboratory, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Aohua ZhangDepartment of Clinical Laboratory, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Weihan ZhengDepartment of Clinical Laboratory, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Jiahui ZhaoDepartment of Clinical Laboratory, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Jun MaDepartment of Clinical Laboratory, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Natural killer (NK) cells are crucial for immune defense against tumors, but their function is often impaired in the tumor microenvironment. High mobility group box 2 (HMGB2), a chromatin-associated protein, is implicated in various cancers, yet its role in regulating NK cells, particularly in esophageal squamous cell carcinoma (ESCC), is unclear. We conducted transcriptomic and proteomic analyses of peripheral blood mononuclear cells (PBMCs) from ESCC patients and healthy donors to identify immunoregulatory molecules. Flow cytometry confirmed upregulation of HMGB2 in NK cells from ESCC patients, correlating with advanced tumor stage. Using RNA interference, CRISPR/Cas9, and overexpression methods, we modulated HMGB2 in NK-92 cells and assessed their cytotoxicity against ESCC cells. HMGB2 silencing or knockout enhanced NK cell cytotoxicity, evidenced by increased granzyme B, perforin, IFN-γ, and TNF-α, and higher tumor cell lysis. Conversely, HMGB2 overexpression suppressed these effects. Mechanistically, HMGB2 ablation induced ANGPT1 expression and activated the PI3K/AKT pathway. ANGPT1 knockdown in KO-HMGB2 NK cells reduced PI3K/AKT activation, confirming the involvement of the ANGPT1/PI3K/AKT axis in enhanced NK cell function. These results indicate that HMGB2 inhibits NK cell-mediated anti-tumor immunity in ESCC. HMGB2 depletion enhances NK cell cytotoxicity via the ANGPT1/PI3K/AKT pathway, suggesting its potential as a therapeutic target to improve NK cell-based immunotherapy in ESCC.

Indexed as

Esophageal NeoplasmsEsophageal Squamous Cell CarcinomaHMGB2 ProteinKiller Cells, NaturalPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktCell Line, TumorCytotoxicity, ImmunologicFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedSignal TransductionHMGB2 ProteinPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktANGPT1CRISPR-Cas9ESCCHMGB2natural killer cellsPI3K/Akt pathway

Identifiers

PMID41280896
PMCPMC12634629

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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.