Evidence map›Paper›PMID 25501829›Full record

ArticleCell death & disease2014

Functional expression cloning identifies COX-2 as a suppressor of antigen-specific cancer immunity.

C Göbel, F Breitenbuecher, H Kalkavan, P S Hähnel, S Kasper, S Hoffarth, K Merches, H Schild, K S Lang, M Schuler

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.6field-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

36 citing papers in PubMed, 45 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Review
  5. Expression ofFrontiers in oncology · 2024
    Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. lncRNA-PACER upregulatesGastroenterology report · 2021
    Article
  11. Prognostic Significance of COX-2 Overexpression inInternational journal of molecular sciences · 2020
    Article
  12. Review
  13. Review
  14. Synergistic Combination of Oncolytic Virotherapy and Immunotherapy for Glioma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
    Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. Article
  20. COX-2 mediates tumor-stromal prolactin signaling to initiate tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
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 at 3 institutions in 1 country.

C GöbelDepartment of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen 45122, Germany.
F BreitenbuecherDepartment of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen 45122, Germany.
H Kalkavan1] Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen 45122, Germany [2] Department of Immunology, University Hospital Essen, University Duisburg-Essen, Essen 45122, Germany.
P S HähnelDepartment of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen 45122, Germany.
S KasperDepartment of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen 45122, Germany.
S HoffarthDepartment of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen 45122, Germany.
K MerchesDepartment of Immunology, University Hospital Essen, University Duisburg-Essen, Essen 45122, Germany.
H SchildInstitute for Immunology, University Medical Center, Mainz 55101, Germany.
K S LangDepartment of Immunology, University Hospital Essen, University Duisburg-Essen, Essen 45122, Germany.
M Schuler1] Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen 45122, Germany [2] German Cancer Consortium (DKTK), Heidelberg 69120, Germany.
University of Duisburg-Essen · DEGerman Cancer Research Center · DEUniversity Medical Center of the Johannes Gutenberg University Mainz · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The efficacy of immune surveillance and antigen-specific cancer immunotherapy equally depends on the activation of a sustained immune response targeting cancer antigens and the susceptibility of cancer cells to immune effector mechanisms. Using functional expression cloning and T-cell receptor (TCR) transgenic mice, we have identified cyclooxygenase 2/prostaglandin-endoperoxide synthase 2 (COX-2) as resistance factor against the cytotoxicity induced by activated, antigen-specific T cells. Expressing COX-2, but not a catalytically inactive COX-2 mutant, increased the clonogenic survival of E1A-transformed murine cancer cells when cocultured with lymphocytes from St42Rag2(-/-) mice harboring a transgenic TCR directed against an E1A epitope. COX-2 expressing tumors established in immune-deficient mice were less susceptible to adoptive immunotherapy with TCR transgenic lymphocytes in vivo. Also, immune surveillance of COX-2-positive tumor cells in TCR transgenic mice was less efficient. The growth of murine MC-GP tumors, which show high endogenous COX-2 expression, in immunocompetent mice was effectively suppressed by treatment with a selective COX-2 inhibitor, celecoxib. Mechanistically, COX-2 expression blunted the interferon-gamma release of antigen-specific T cells exposed to their respective cellular targets, and increased the expression of interleukin-4 and indoleamine 2,3-dioxygenase by tumor cells. Addition of interferon-gamma sensitized COX-2 expressing cancer cells to tumor suppression by antigen-specific T cells. In conclusion, COX-2, which is frequently induced in colorectal cancer, contributes to immune evasion and resistance to antigen-specific cancer immunotherapy by local suppression of T-cell effector functions.

Indexed as

AnimalsCD8-Positive T-LymphocytesCyclooxygenase 2Cytotoxicity, ImmunologicHumansImmunotherapy, AdoptiveIndoleamine-Pyrrole 2,3,-DioxygenaseInterferon-gammaInterleukin-4MiceMice, Inbred C57BLMice, SCIDMice, TransgenicNeoplasmsReceptors, Antigen, T-CellSpecies SpecificityCyclooxygenase 2Indoleamine-Pyrrole 2,3,-DioxygenaseInterferon-gammaInterleukin-4Receptors, Antigen, T-Cell

Identifiers

PMID25501829
PMCPMC4649842
OpenAlexW2012045910

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.