Evidence map›Paper›PMID 41486114›Full record

ArticleJournal of biomedical science2026

High-CD14-expressing urothelial cancer cells foster a neutrophil-rich tumor microenvironment that increases the risk of radiation-promoted distant metastasis.

Yun Chiang, Yu-Chieh Tsai, Chung-Chieh Wang, Fu-Jen Hsueh, Chao-Yuan Huang, Chung-Hsin Chen, Yeong-Shiau Pu, Shih-Chieh Chueh, Xavier Cheng-Hong Tsai, Jason Chia-Hsien Cheng

Abstract read
In one paragraph

Article in Journal of biomedical science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
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

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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

2 citing papers in PubMed.

  1. Article
  2. Review
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

10 authors.

Yun ChiangGraduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
Yu-Chieh TsaiGraduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
Chung-Chieh WangDepartment of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
Fu-Jen HsuehGraduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
Chao-Yuan HuangDepartment of Urology, National Taiwan University Hospital, Taipei, Taiwan.
Chung-Hsin ChenDepartment of Urology, National Taiwan University Hospital, Taipei, Taiwan.
Yeong-Shiau PuDepartment of Urology, National Taiwan University Hospital, Taipei, Taiwan.
Shih-Chieh ChuehDepartment of Urology, National Taiwan University Hospital, Taipei, Taiwan.
Xavier Cheng-Hong TsaiDivision of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Jason Chia-Hsien ChengGraduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan. jasoncheng@ntu.edu.tw.

Funding

National Science and Technology Council MOST 110-2314-B-002-147-MY3National Science and Technology Council MOST 112-2314-B-002-116-MY3National Taiwan University Cancer Center NTUCCS 113-08National Taiwan University Hospital NTUH 112-O0005
6 · The paper itself

Abstract

backgroundRadiation (RT)-promoted distant metastasis (DM) is an underrecognized complication that can compromise the therapeutic efficacy of local RT. This study aimed to identify tumor microenvironment (TME) traits that predispose to RT-promoted DM and provide mechanistic insights for potential therapeutic intervention.

methodsWe performed NanoString analysis on tumor samples from urothelial cancer patients to compare the TME profiles of those with and without RT-promoted DM. To complement clinical findings, we conducted RNA sequencing (RNAseq) of murine bladder cancer cell lines, MB49 (with RT-promoted DM) and MBT2 (without), followed by in vivo ectopic tumor modeling, flow cytometry of immune cell infiltrates, and cytokine array profiling.

resultsNanoString analysis revealed a significant enrichment of C-X-C motif receptor 2 (CXCR2)-expressing neutrophils in the TME of patients with RT-promoted DM. These tumors also exhibited nuclear factor kappa B (NFκB) activation and increased secretion of neutrophil-recruiting chemokines. RNAseq and cytokine profiling identified CD14 expression in tumor cells as a key upstream regulator of neutrophilic TME via NFκB signaling. The use of antagonists to block neutrophils and inhibit CD14 expression in cancer cells, which reduces the secretion of neutrophil-recruiting chemokines, effectively mitigated RT-promoted DM in both the MB49 and LLC mouse models.

conclusionsCD14 expression in tumor cells plays a pivotal role in shaping a neutrophil-enriched TME, which increases the susceptibility to RT-promoted DM. CD14 represents a potential predictive biomarker and therapeutic target for mitigating this adverse outcome.

Indexed as

Lipopolysaccharide ReceptorsNeoplasms, Radiation-InducedNeutrophilsTumor MicroenvironmentUrinary Bladder NeoplasmsAnimalsCell Line, TumorChemokinesDisease Models, AnimalMaleMiceMice, Inbred C57BLNeoplasm MetastasisNF-kappa BReceptors, Interleukin-8BUrotheliumChemokinesCxcr2 protein, mouseLipopolysaccharide ReceptorsNF-kappa BReceptors, Interleukin-8BCD14MetastasisNeutrophilRadiotherapyTumor microenvironment

Identifiers

PMID41486114
PMCPMC12765301

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Registered trials

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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.