Evidence map›Paper›PMID 34112803›Full record

ArticleNature communications2021

Tumor microenvironmental cytokines bound to cancer exosomes determine uptake by cytokine receptor-expressing cells and biodistribution.

Luize G Lima, Sunyoung Ham, Hyunku Shin, Edna P Z Chai, Erica S H Lek, Richard J Lobb, Alexandra F Müller, Suresh Mathivanan, Belinda Yeo, Yeonho Choi and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed, 1 pooled it
7.8field-weighted citation impact, top 2% 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

99 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Molecular Mechanisms and Immune Regulation in Prostate Cancer: A Review.International journal of molecular sciences · 2026
    Review
  4. Review
  5. Exosome-mediated siRNA delivery in cancer: Loading strategies, targeting approaches, and therapeutic outcomes.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Extracellular vesicles in spine tumors: biological roles, immune modulation, and therapeutic implications.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026
    Review
  14. Article
  15. Article
  16. Does extracellular vesicle specificity truly exist?Cell communication and signaling : CCS · 2026
    Review
  17. Article
  18. Article
  19. Review
  20. Review

39 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

12 authors at 7 institutions in 2 countries.

Luize G Lima *Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
Sunyoung Ham *Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
Hyunku ShinDepartment of Bio-convergence Engineering, Korea University, Seoul, South Korea.
Edna P Z ChaiTumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
Erica S H LekTumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
Richard J LobbTumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.ORCID 0000-0001-9548-8843
Alexandra F MüllerTumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
Suresh MathivananDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia.ORCID 0000-0002-7290-5795
Belinda YeoOlivia Newton-John Cancer Research Institute, Austin Hospital, Heidelberg, Melbourne, VIC, Australia.
Yeonho ChoiDepartment of Bio-convergence Engineering, Korea University, Seoul, South Korea.ORCID 0000-0001-8590-3468
Belinda S ParkerCancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.ORCID 0000-0002-8333-1926
Andreas MöllerTumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia. andreas.moller@qimrberghofer.edu.au.ORCID 0000-0002-8618-6998
QIMR Berghofer Medical Research Institute · AUKorea University · KRQueensland University of Technology · AUThe University of Queensland · AUAustin Hospital · AULa Trobe University · AUThe University of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metastatic spread of a cancer to secondary sites is a coordinated, non-random process. Cancer cell-secreted vesicles, especially exosomes, have recently been implicated in the guidance of metastatic dissemination, with specific surface composition determining some aspects of organ-specific localization. Nevertheless, whether the tumor microenvironment influences exosome biodistribution has yet to be investigated. Here, we show that microenvironmental cytokines, particularly CCL2, decorate cancer exosomes via binding to surface glycosaminoglycan side chains of proteoglycans, causing exosome accumulation in specific cell subsets and organs. Exosome retention results in changes in the immune landscape within these organs, coupled with a higher metastatic burden. Strikingly, CCL2-decorated exosomes are directed to a subset of cells that express the CCL2 receptor CCR2, demonstrating that exosome-bound cytokines are a crucial determinant of exosome-cell interactions. In addition to the finding that cytokine-conjugated exosomes are detected in the blood of cancer patients, we discovered that healthy subjects derived exosomes are also associated with cytokines. Although displaying a different profile from exosomes isolated from cancer patients, it further indicates that specific combinations of cytokines bound to exosomes could likewise affect other physiological and disease settings.

Indexed as

Tumor MicroenvironmentAnimalsBreast NeoplasmsChemokine CCL2CytokinesExosomesFemaleGlycosaminoglycansHumansKiller Cells, NaturalLiverLungMacrophagesMiceMice, Inbred C57BLNeoplasm MetastasisCCL2 protein, humanCCR2 protein, humanChemokine CCL2CytokinesGlycosaminoglycansProteoglycansReceptors, CCR2Receptors, Cytokine

Identifiers

PMID34112803
PMCPMC8192925
OpenAlexW3173043499

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.