Evidence map›Paper›PMID 34354077›Full record

ArticleNature communications2021

Viral vector-mediated reprogramming of the fibroblastic tumor stroma sustains curative melanoma treatment.

Sandra S Ring, Jovana Cupovic, Lucas Onder, Mechthild Lütge, Christian Perez-Shibayama, Cristina Gil-Cruz, Elke Scandella, Angelina De Martin, Urs Mörbe, Fabienne Hartmann and 10 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 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

18 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Cytokines and cancer-associated fibroblasts.Journal of hematology & oncology · 2026
    Review
  6. Article
  7. Review
  8. Article
  9. Lymphoid stroma in all its states.Frontiers in immunology · 2025
    Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
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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

20 authors at 4 institutions in 2 countries.

Sandra S RingInstitute of Immunobiology, Kantonsspital St.Gallen, St.Gallen, Switzerland.
Jovana CupovicInstitute of Immunobiology, Kantonsspital St.Gallen, St.Gallen, Switzerland.
Lucas OnderInstitute of Immunobiology, Kantonsspital St.Gallen, St.Gallen, Switzerland.
Mechthild LütgeInstitute of Immunobiology, Kantonsspital St.Gallen, St.Gallen, Switzerland.ORCID 0000-0001-9011-5319
Christian Perez-ShibayamaInstitute of Immunobiology, Kantonsspital St.Gallen, St.Gallen, Switzerland.
Cristina Gil-CruzInstitute of Immunobiology, Kantonsspital St.Gallen, St.Gallen, Switzerland.
Elke ScandellaInstitute of Immunobiology, Kantonsspital St.Gallen, St.Gallen, Switzerland.
Angelina De MartinInstitute of Immunobiology, Kantonsspital St.Gallen, St.Gallen, Switzerland.
Urs MörbeInstitute of Immunobiology, Kantonsspital St.Gallen, St.Gallen, Switzerland.ORCID 0000-0001-8747-437X
Fabienne HartmannInstitute of Immunobiology, Kantonsspital St.Gallen, St.Gallen, Switzerland.ORCID 0000-0003-2247-2693
Robert WengerDepartment of Plastic Reconstructive Surgery, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Matthias SpieglDepartment of Plastic Reconstructive Surgery, Kantonsspital St. Gallen, St. Gallen, Switzerland.ORCID 0000-0003-3940-7791
Andrej BesseDepartment of Medical Oncology and Hematology, Kantonsspital St.Gallen, St.Gallen, Switzerland.
Weldy V BonillaDivision of Experimental Virology, Department of Biomedicine, University of Basel, Basel, Switzerland.
Felix StemesederHookipa Pharma Inc., New York, USA.
Sarah SchmidtHookipa Pharma Inc., New York, USA.
Klaus K OrlingerHookipa Pharma Inc., New York, USA.
Philippe KrebsInstitute of Pathology, University of Berne, Berne, Switzerland.ORCID 0000-0003-4918-6654
Burkhard LudewigInstitute of Immunobiology, Kantonsspital St.Gallen, St.Gallen, Switzerland. burkhard.ludewig@kssg.ch.ORCID 0000-0002-7685-573X
Lukas FlatzInstitute of Immunobiology, Kantonsspital St.Gallen, St.Gallen, Switzerland. lukas.flatz@kssg.ch.
Kantonsspital St. Gallen · CHUniversity of Basel · CHUniversity of Bern · CHUniversity of Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The tumor microenvironment (TME) is a complex amalgam of tumor cells, immune cells, endothelial cells and fibroblastic stromal cells (FSC). Cancer-associated fibroblasts are generally seen as tumor-promoting entity. However, it is conceivable that particular FSC populations within the TME contribute to immune-mediated tumor control. Here, we show that intratumoral treatment of mice with a recombinant lymphocytic choriomeningitis virus-based vaccine vector expressing a melanocyte differentiation antigen resulted in T cell-dependent long-term control of melanomas. Using single-cell RNA-seq analysis, we demonstrate that viral vector-mediated transduction reprogrammed and activated a Cxcl13-expressing FSC subset that show a pronounced immunostimulatory signature and increased expression of the inflammatory cytokine IL-33. Ablation of Il33 gene expression in Cxcl13-Cre-positive FSCs reduces the functionality of intratumoral T cells and unleashes tumor growth. Thus, reprogramming of FSCs by a self-antigen-expressing viral vector in the TME is critical for curative melanoma treatment by locally sustaining the activity of tumor-specific T cells.

Indexed as

AnimalsAntigens, NeoplasmCancer-Associated FibroblastsCancer VaccinesCellular Reprogramming TechniquesChemokine CXCL13FemaleGenetic VectorsInterleukin-33Intramolecular OxidoreductasesLymphocytic choriomeningitis virusMelanoma, ExperimentalMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicAntigens, NeoplasmCancer VaccinesChemokine CXCL13Cxcl13 protein, mousedopachrome isomeraseIl33 protein, mouseInterleukin-33Intramolecular Oxidoreductases

Identifiers

PMID34354077
PMCPMC8342618
OpenAlexW3187993652

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.