Evidence map›Paper›PMID 34518296›Full record

ArticleMolecular cancer therapeutics2021

Targeting Tumor-Stromal IL6/STAT3 Signaling through IL1 Receptor Inhibition in Pancreatic Cancer.

Austin R Dosch, Samara Singh, Xizi Dai, Siddharth Mehra, Iago De Castro Silva, Anna Bianchi, Supriya Srinivasan, Zhen Gao, Yuguang Ban, Xi Chen and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cancer therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.5field-weighted citation impact, top 5% 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

34 citing papers in PubMed, 52 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Dynamic feedback between IL-6 and TWIST1 drives pancreatic cancer progression.Translational gastroenterology and hepatology · 2026
    Article
  5. Review
  6. CAR-Macrophage Cell Therapy: A New Era of Hope for Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024
    Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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

14 authors at 1 institution in 1 country.

Austin R DoschDivision of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Samara SinghDivision of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Xizi DaiDivision of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida.ORCID 0000-0003-3183-545X
Siddharth MehraDivision of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Iago De Castro SilvaDivision of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Anna BianchiDivision of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Supriya SrinivasanDivision of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Zhen GaoDepartment of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida.ORCID 0000-0003-3461-1910
Yuguang BanDepartment of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida.
Xi ChenDepartment of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida.
Sulagna BanerjeeDivision of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida.ORCID 0000-0003-2338-1662
Nagaraj S NagathihalliDivision of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Jashodeep DattaDivision of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida.ORCID 0000-0002-5052-7586
Nipun B MerchantDivision of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida. nmerchant@miami.edu.
University of Miami · US

Funding

Tumor Biology Research ProgramP30CA240139 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI George S. Grills · 2019 to 2026
$24.1M
Miami Clinical and Translational Science InstituteUL1TR002736 · NCATS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI CARRASQUILLO, OLVEEN, KOBETZ, ERIN N · 2018 to 2022
$23.2M
Stat3 Signaling in Pancreas CancerR01CA161976 · NCI · VANDERBILT UNIVERSITY · PI MERCHANT, NIPUN B. · 2012 to 2022
$3.4M
Research Training Program in Surgical OncologyT32CA211034 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI MERCHANT, NIPUN B. · 2016 to 2025
$2.7M
Combining Immunotherapy with Urolithin A to Improve Pancreatic Cancer SurvivalR03CA249401 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI NAGATHIHALLI, NAGARAJ S. · 2020 to 2021
$154k
NCATS NIH HHS UL1 TR002736NCI NIH HHS P30 CA240139NCI NIH HHS R01 CA161976NCI NIH HHS R03 CA249401NCI NIH HHS T32 CA211034
6 · The paper itself

Abstract

A hallmark of pancreatic ductal adenocarcinoma (PDAC) is the presence of a dense, desmoplastic stroma and the consequent altered interactions between cancer cells and their surrounding tumor microenvironment (TME) that promote disease progression, metastasis, and chemoresistance. We have previously shown that IL6 secreted from pancreatic stellate cells (PSC) stimulates the activation of STAT3 signaling in tumor cells, an established mechanism of therapeutic resistance in PDAC. We have now identified the tumor cell-derived cytokine IL1α as an upstream mediator of IL6 release from PSCs that is involved in STAT3 activation within the TME. Herein, we show that IL1α is overexpressed in both murine and human PDAC tumors and engages with its cognate receptor IL1R1, which is strongly expressed on stromal cells. Further, we show that IL1R1 inhibition using anakinra (recombinant IL1 receptor antagonist) significantly reduces stromal-derived IL6, thereby suppressing IL6-dependent STAT3 activation in human PDAC cell lines. Anakinra treatment results in significant reduction in IL6 and activated STAT3 levels in pancreatic tumors from

Indexed as

AnimalsHumansInterleukin-6MicePancreatic NeoplasmsReceptors, Interleukin-1Signal TransductionInterleukin-6Receptors, Interleukin-1

Identifiers

PMID34518296
PMCPMC8571047
OpenAlexW3199237048

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.