Evidence map›Paper›PMID 34290237›Full record

ArticleNPJ breast cancer2021

IL-1B drives opposing responses in primary tumours and bone metastases; harnessing combination therapies to improve outcome in breast cancer.

Claudia Tulotta, Diane V Lefley, Charlotte K Moore, Ana E Amariutei, Amy R Spicer-Hadlington, Lewis A Quayle, Russell O Hughes, Khawla Ahmed, Victoria Cookson, Catherine A Evans and 6 more

Open access · goldAbstract read
In one paragraph

Article in NPJ breast cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.9field-weighted citation impact, top 4% 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

42 citing papers in PubMed, 61 citations in OpenAlex.

  1. Review
  2. Article
  3. Mechanisms of breast cancer dormancy in bone metastasis.Clinical & experimental metastasis · 2026
    Review
  4. Review
  5. Review
  6. Interplay of Interleukin-1Oncology research · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Cancer Cell Dormancy in the Bone Microenvironment.Current osteoporosis reports · 2025
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review
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

16 authors at 4 institutions in 1 country.

Claudia TulottaDepartment of Oncology and Metabolism, Weston Park Cancer Centre, University of Sheffield, Sheffield, UK.ORCID http://orcid.org/0000-0002-4554-3709
Diane V LefleyDepartment of Oncology and Metabolism, Weston Park Cancer Centre, University of Sheffield, Sheffield, UK.ORCID http://orcid.org/0000-0002-4766-757X
Charlotte K MooreDepartment of Oncology and Metabolism, Weston Park Cancer Centre, University of Sheffield, Sheffield, UK.
Ana E AmariuteiDepartment of Oncology and Metabolism, Weston Park Cancer Centre, University of Sheffield, Sheffield, UK.ORCID http://orcid.org/0000-0001-5803-1166
Amy R Spicer-HadlingtonDepartment of Oncology and Metabolism, Weston Park Cancer Centre, University of Sheffield, Sheffield, UK.ORCID http://orcid.org/0000-0001-6474-1498
Lewis A QuayleDepartment of Oncology and Metabolism, Weston Park Cancer Centre, University of Sheffield, Sheffield, UK.ORCID http://orcid.org/0000-0002-6394-4186
Russell O HughesDepartment of Oncology and Metabolism, Weston Park Cancer Centre, University of Sheffield, Sheffield, UK.
Khawla AhmedDepartment of Oncology and Metabolism, Weston Park Cancer Centre, University of Sheffield, Sheffield, UK.
Victoria CooksonDepartment of Oncology and Metabolism, Weston Park Cancer Centre, University of Sheffield, Sheffield, UK.ORCID http://orcid.org/0000-0003-3089-4837
Catherine A EvansDepartment of Oncology and Metabolism, Weston Park Cancer Centre, University of Sheffield, Sheffield, UK.
Jayakumar VadakekolathuJohn van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK.ORCID http://orcid.org/0000-0002-2671-4285
Paul HeathSheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK.ORCID http://orcid.org/0000-0002-8385-1438
Sheila FrancisDepartment of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
Emmanuel PinteauxFaculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-9986-4401
A Graham PockleyJohn van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK.ORCID http://orcid.org/0000-0001-9593-6431
Penelope D OttewellDepartment of Oncology and Metabolism, Weston Park Cancer Centre, University of Sheffield, Sheffield, UK. p.d.ottewell@sheffield.ac.uk.ORCID http://orcid.org/0000-0002-4826-0771
Weston Park Cancer Centre · GBNottingham Trent University · GBUniversity of Sheffield · GBUniversity of Manchester · GB

Funding

British Heart Foundation PG/13/55/30365British Heart Foundation PG/20/10010Medical Research Council MR/P000096/1
6 · The paper itself

Abstract

Breast cancer bone metastasis is currently incurable, ~75% of patients with late-stage breast cancer develop disease recurrence in bone and available treatments are only palliative. We have previously shown that production of the pro-inflammatory cytokine interleukin-1B (IL-1B) by breast cancer cells drives bone metastasis in patients and in preclinical in vivo models. In the current study, we have investigated how IL-1B from tumour cells and the microenvironment interact to affect primary tumour growth and bone metastasis through regulation of the immune system, and whether targeting IL-1 driven changes to the immune response improves standard of care therapy for breast cancer bone metastasis. Using syngeneic IL-1B/IL1R1 knock out mouse models in combination with genetic manipulation of tumour cells to overexpress IL-1B/IL1R1, we found that IL-1B signalling elicited an opposite response in primary tumours compared with bone metastases. In primary tumours, IL-1B inhibited growth, by impairing the infiltration of innate immune cell subsets with potential anti-cancer functions but promoted enhanced tumour cell migration. In bone, IL-1B stimulated the development of osteolytic metastases. In syngeneic models of breast cancer, combining standard of care treatments (Doxorubicin and Zoledronic acid) with the IL-1 receptor antagonist Anakinra inhibited both primary tumour growth and metastasis. Anakinra had opposite effects on the immune response compared to standard of care treatment, and its anti-inflammatory signature was maintained in the combination therapy. These data suggest that targeting IL-1B signalling may provide a useful therapeutic approach to inhibit bone metastasis and improve efficacy of current treatments for breast cancer patients.

Identifiers

PMID34290237
PMCPMC8295314
OpenAlexW3186178212

What OpenQuestion holds

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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.