Evidence map›Paper›PMID 39330930›Full record

ArticleJournal of extracellular vesicles2024

MAP kinase kinase 1 (MEK1) within extracellular vesicles inhibits tumour growth by promoting anti-tumour immunity.

Stephen C Searles, Wei-Shan Chen, Jarrod D Yee, Preston Lee, Calvin K Lee, Christine Caron, Felippe Neto, Irina Matei, David Lyden, Jack D Bui

Erratum issuedAbstract read
In one paragraph

Article in Journal of extracellular vesicles, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Stephen C SearlesDepartment of Pathology, University of California, San Diego, California, USA.
Wei-Shan ChenDepartment of Pathology, University of California, San Diego, California, USA.
Jarrod D YeeDepartment of Pathology, University of California, San Diego, California, USA.
Preston LeeDepartment of Pathology, University of California, San Diego, California, USA.
Calvin K LeeDepartment of Pathology, University of California, San Diego, California, USA.
Christine CaronDepartment of Pathology, University of California, San Diego, California, USA.
Felippe NetoDepartment of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York, USA.
Irina MateiDepartment of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York, USA.
David LydenDepartment of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York, USA.
Jack D BuiDepartment of Pathology, University of California, San Diego, California, USA.ORCID 0000-0002-9324-368X

Funding

The Hartwell Foundation Biomedical Research Collaboration Award
6 · The paper itself

Abstract

Extracellular vesicles (EVs) mediate intercellular communication in many physiologic processes and can modulate immune responses in individuals with cancer. Most studies of EVs in cancer have focused on their tumour promoting properties. Whether and how EVs might mediate tumour regression besides carrying antigens has not been well characterized. Using a mouse model of highly immunogenic regressor versus poorly immunogenic progressor tumour cells, we have characterized the role of EVs in activating macrophages and promoting tumour rejection. We found that the signalling molecule MAP2K1 (MEK1) is enriched in EVs secreted by regressor relative to progressor cells. Progressor EVs engineered to have levels of MEK1 similar to regressor EVs could inhibit tumour growth by indirectly promoting adaptive immunity in both syngeneic and 3rd party tumours. This effect required MEK1 activity and could occur by activating macrophages to promote adaptive immune responses against the tumour via the cytokine interferon-gamma. Our results suggest that MEK inhibition may be deleterious to cancer treatment, since MEK1 plays an important cell-extrinsic, tumour-suppressive role within EVs. Moreover, the delivery of MEK1 to tumour-associated macrophages, either by EVs, nanoparticles, or some other means, could be a useful strategy to treat cancer via the activation of anti-tumour immunity.

Indexed as

Extracellular VesiclesMAP Kinase Kinase 1Adaptive ImmunityAnimalsCell Line, TumorCell ProliferationFemaleHumansInterferon-gammaMacrophagesMiceMice, Inbred C57BLNeoplasmsInterferon-gammaMap2k1 protein, mouseMAP Kinase Kinase 1extracellular vesiclesmacrophagesMEK1regressors

Identifiers

PMID39330930
PMCPMC11428867

What OpenQuestion holds

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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.