Evidence map›Paper›PMID 30459756›Full record

ArticleFrontiers in immunology2018

Hypoxia Modifies the Transcriptome of Human NK Cells, Modulates Their Immunoregulatory Profile, and Influences NK Cell Subset Migration.

Monica Parodi, Federica Raggi, Davide Cangelosi, Claudia Manzini, Mirna Balsamo, Fabiola Blengio, Alessandra Eva, Luigi Varesio, Gabriella Pietra, Lorenzo Moretta and 3 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed
5.6field-weighted citation impact, top 3% of its field
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

105 citing papers in PubMed, 137 citations in OpenAlex.

  1. DRP1 depletion protects NK cells from hypoxia-induced dysfunction.Redox report : communications in free radical research · 2026
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45 more citing papers are in PubMed but not listed here.

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

13 authors at 4 institutions in 1 country.

Monica ParodiUOC Immunologia, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
Federica RaggiLaboratorio di Biologia Molecolare, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Davide CangelosiLaboratorio di Biologia Molecolare, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Claudia ManziniLaboratorio di Immunologia Clinica e Sperimentale, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Mirna BalsamoDipartimento di Medicina Sperimentale, Università di Genova, Genova, Italy.
Fabiola BlengioLaboratorio di Biologia Molecolare, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Alessandra EvaLaboratorio di Biologia Molecolare, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Luigi VaresioLaboratorio di Biologia Molecolare, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Gabriella PietraUOC Immunologia, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
Lorenzo MorettaImmunology Area, Ospedale Pediatrico Bambin Gesù, Rome, Italy.
Maria Cristina MingariUOC Immunologia, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
Massimo VitaleUOC Immunologia, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
Maria Carla BoscoLaboratorio di Biologia Molecolare, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Istituto Giannina Gaslini · ITOspedale Policlinico San Martino · ITUniversity of Genoa · ITIstituti di Ricovero e Cura a Carattere Scientifico · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypoxia, which characterizes most tumor tissues, can alter the function of different immune cell types, favoring tumor escape mechanisms. In this study, we show that hypoxia profoundly acts on NK cells by influencing their transcriptome, affecting their immunoregulatory functions, and changing the chemotactic responses of different NK cell subsets. Exposure of human peripheral blood NK cells to hypoxia for 16 or 96 h caused significant changes in the expression of 729 or 1,100 genes, respectively. Gene Set Enrichment Analysis demonstrated that these changes followed a consensus hypoxia transcriptional profile. As assessed by Gene Ontology annotation, hypoxia-targeted genes were implicated in several biological processes: metabolism, cell cycle, differentiation, apoptosis, cell stress, and cytoskeleton organization. The hypoxic transcriptome also showed changes in genes with immunological relevance including those coding for proinflammatory cytokines, chemokines, and chemokine-receptors. Quantitative RT-PCR analysis confirmed the modulation of several immune-related genes, prompting further immunophenotypic and functional studies. Multiplex ELISA demonstrated that hypoxia could variably reduce NK cell ability to release IFNγ, TNFα, GM-CSF, CCL3, and CCL5 following PMA+Ionomycin or IL15+IL18 stimulation, while it poorly affected the response to IL12+IL18. Cytofluorimetric analysis showed that hypoxia could influence NK chemokine receptor pattern by sustaining the expression of CCR7 and CXCR4. Remarkably, this effect occurred selectively (CCR7) or preferentially (CXCR4) on CD56

Indexed as

TranscriptomeCell DifferentiationCell MovementChemotaxisCytokinesFlow CytometryGene Expression ProfilingGene Expression RegulationHumansHypoxiaImmunomodulationKiller Cells, NaturalLymphocyte ActivationCytokinesCD56bright cellschemokine receptorscytokines/chemokineshypoxiaNK cellstranscriptometumor immunologytumor infiltration

Identifiers

PMID30459756
PMCPMC6232835
OpenAlexW2896521195

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.