Evidence map›Paper›PMID 42273225›Full record

ReviewResearch (Washington, D.C.)2026

Extracellular Metabolites and Natural Killer Cell Antitumor Function: Mechanisms and Therapeutic Strategies.

Ruichen Zang, Chen Zhang, Yutian Fu, Juntong Chen, Yicheng Chen, Yanlan Yu, Bufu Tang, Jie Zhang, Guoqing Ding

Abstract readReview
In one paragraph

Review in Research (Washington, D.C.), 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
0cells of the map it votes in
0citing 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

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

9 authors.

Ruichen ZangDepartment of Urology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.ORCID https://orcid.org/0009-0003-3288-3661
Chen ZhangDepartment of Urology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.ORCID https://orcid.org/0009-0009-5447-8978
Yutian FuDepartment of Urology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Juntong ChenDepartment of Urology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Yicheng ChenDepartment of Urology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.ORCID https://orcid.org/0000-0003-1351-7896
Yanlan YuDepartment of Urology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.ORCID https://orcid.org/0000-0003-3156-3618
Bufu TangDepartment of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.
Jie ZhangDepartment of Urology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.ORCID https://orcid.org/0000-0002-9957-077X
Guoqing DingDepartment of Urology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.ORCID https://orcid.org/0000-0003-3156-3618

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Natural killer (NK) cells are innate cytotoxic lymphocytes capable of eliminating malignant cells independent of prior antigen sensitization, thereby constituting a critical first-line defense in tumor immunosurveillance. Within the tumor microenvironment (TME), metabolic dysregulation profoundly impairs NK cell effector function, and accumulating studies have investigated the regulatory effects of extracellular metabolites on NK cells. This review systematically delineates the direct mechanistic interplay between extracellular metabolites and NK cell antitumor immunity, with particular emphasis on their roles as structural components, bioenergetic substrates, metabolic reprogramming inducers, modification donors, gene transcription regulators, stress response mediators, intracellular pH modulators, and ligands engaging cognate receptors to initiate downstream signaling cascades. Furthermore, we discuss the therapeutic strategies targeting metabolites to potentiate NK cell functionality, encompassing modulation of metabolite availability within the TME and exploitation of metabolite-sensitive signaling axes. In addition, combination of metabolic interventions with other modalities, such as adoptive NK cell transfer and anti-programmed cell death protein 1/programmed death-ligand 1 therapy, is also evaluated for prospective applications. This review provides a conceptual framework for understanding the metabolic regulation of NK cells, highlighting emerging directions for advancing NK-cell-centered cancer immunotherapy through metabolic modulation.

Identifiers

PMID42273225
PMCPMC13247316

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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.