Evidence mapPaperPMID 42094009Full record

ReviewFrontiers in immunology2026

Orchestration of the tumor microenvironment by citrus flavonoids: from preclinical mechanisms to translational therapeutic.

Siyao Ma, Xuebing Wang, Mingzhu Li, Wenping Wang, Yanyi Ren, Yue Shen, Ke Yang, Ze Zhang, Zitong Feng, Shuhan Tang

Abstract readReview
In one paragraph

Review in Frontiers in immunology, 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

10 authors.

Siyao MaThe First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Xuebing WangLiaoning Cancer Hospital and Institute, Cancer Hospital of Dalian University of Technology, Shenyang, China.
Mingzhu LiLiaoning Cancer Hospital and Institute, Cancer Hospital of Dalian University of Technology, Shenyang, China.
Wenping WangLiaoning Cancer Hospital and Institute, Cancer Hospital of Dalian University of Technology, Shenyang, China.
Yanyi RenLiaoning Cancer Hospital and Institute, Cancer Hospital of Dalian University of Technology, Shenyang, China.
Yue ShenThe First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Ke YangThe First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Ze ZhangThe First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Zitong FengThe First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Shuhan TangThe First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Malignant lung tumors are the leading cause of cancer-related mortality worldwide, and therefore remodeling of the tumor microenvironment (TME) has become an important strategy to overcome anti-tumor therapy resistance in lung cancer. Flavonoid components isolated from Citri Reticulatae Pericarpium (CRP), such as nobiletin, hesperidin, and tangeretin, have been shown to modulate the lung cancer TME in a highly relevant manner. The present narrative review collected literature from the PubMed, Web of Science, Embase, CNKI, and Wanfang databases between 2016 and 2026, and hence discussed the molecular mechanisms by which CRP flavonoids reshape the lung cancer TME, namely their regulation of oxidative stress-inflammation homeostasis, correction of lipid metabolic reprogramming, induction of pyroptosis, and inhibition of epithelial-mesenchymal transition. Discussion of the role of EMT and tumor angiogenesis suppression were also presented. Then evidence regarding the modulation of emerging targets was introduced, namely ferroptosis and the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, which are both promising targets in lung cancer models. Translational prospects of CRP flavonoids were led to enhancing immune checkpoint inhibitor (ICI) efficacy and developing nano-delivery systems. The article first outlined the fundamental barriers, then gave a very systematic and critical review of the contradictory findings, context-dependent effects, and methodological limitations in the existing literature; and then pointed out the gaps in frontier research. Therefore, it provides an excellent theoretical foundation for the research and development of anti-lung cancer drugs from CRP flavonoids, while also objectively identifying the current knowledge gaps and clinical translation bottlenecks.

Indexed as

CitrusFlavonoidsLung NeoplasmsTumor MicroenvironmentAnimalsEpithelial-Mesenchymal TransitionHumansTranslational Research, BiomedicalFlavonoidsCitri Reticulatae Pericarpium (CRP)clinical translationflavonoidslung cancernarrative reviewtumor microenvironment

Identifiers

PMID42094009
PMCPMC13139134

What Socratic holds

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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 Socratic graph.