Evidence map›Paper›PMID 33939146›Full record

ArticleDigestive diseases and sciences2022

Inhibition of TLR7 and TLR9 Reduces Human Cholangiocarcinoma Cell Proliferation and Tumor Development.

Fatma El Zahraa Mohamed, Rajiv Jalan, Shane Minogue, Fausto Andreola, Abeba Habtesion, Andrew Hall, Alison Winstanley, Steven Olde Damink, Massimo Malagó, Nathan Davies and 5 more

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Article in Digestive diseases and sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. TLR9: A Double-Dealing Toll-Like Receptor.ImmunoTargets and therapy · 2025
    Review
  3. Article
  4. Review
  5. Review
  6. 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

15 authors at 3 institutions in 2 countries.

Fatma El Zahraa MohamedUCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
Rajiv JalanUCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
Shane MinogueUCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
Fausto AndreolaUCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
Abeba HabtesionUCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
Andrew HallUCL Institute for Liver and Digestive Health, Royal Free London NHS Foundation Trust, London, UK.
Alison WinstanleyDepartment of Cellular Pathology, University College London Hospitals NHS Foundation Trust, London, UK.
Steven Olde DaminkAcademic Department of Surgery and Interventional Sciences, Royal Free Hospital, London, UK.
Massimo MalagóAcademic Department of Surgery and Interventional Sciences, Royal Free Hospital, London, UK.
Nathan DaviesUCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
Tu Vinh LuongDepartment of Cellular Pathology, Royal Free London NHS Foundation Trust, London, UK.
Amar DhillonDepartment of Cellular Pathology, Royal Free London NHS Foundation Trust, London, UK.
Rajeshwar MookerjeeUCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
Dipok DharUCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
Rajai Munir Al-JehaniUCL Institute for Liver and Digestive Health, Royal Free London NHS Foundation Trust, London, UK. r.al-jehani@ucl.ac.uk.ORCID 0000-0002-1046-4058
The Royal Free Hospital · GBRoyal Free London NHS Foundation Trust · GBUniversity College London Hospitals NHS Foundation Trust · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundToll-like receptors (TLRs) are key players in innate immunity and modulation of TLR signaling has been demonstrated to profoundly affect proliferation and growth in different types of cancer. However, the role of TLRs in human intrahepatic cholangiocarcinoma (ICC) pathogenesis remains largely unexplored.

aimsWe set out to determine if TLRs play any role in ICCs which could potentially make them useful treatment targets.

methodsTissue microarrays containing samples from 9 human ICCs and normal livers were examined immunohistochemically for TLR4, TLR7, and TLR9 expression. Proliferation of human ICC cell line HuCCT1 was measured by MTS assay following treatment with CpG-ODN (TLR9 agonist), imiquimod (TLR7 agonist), chloroquine (TLR7 and TLR9 inhibitor) and IRS-954 (TLR7 and TLR9 antagonist). The in vivo effects of CQ and IRS-954 on tumor development were also examined in a NOD-SCID mouse xenograft model of human ICC.

resultsTLR4 was expressed in all normal human bile duct epithelium but absent in the majority (60%) of ICCs. TLR7 and TLR9 were expressed in 80% of human ICCs. However, TLR7 was absent in all cases of normal human bile duct epithelium and only one was TLR9 positive. HuCCT1 cell proliferation in vitro significantly increased following IMQ or CpG-ODN treatment (P < 0.03 and P < 0.002, respectively) but decreased with CQ (P < 0.02). In the mouse xenograft model there was significant reduction in size of tumors from CQ and IRS-954 treated mice compared to untreated controls.

conclusionTLR7 and TLR9 should be further explored for their potential as actionable targets in the treatment of ICC.

Indexed as

Bile Duct NeoplasmsCholangiocarcinomaAnimalsBile Ducts, IntrahepaticCell ProliferationHumansMiceMice, Inbred NODMice, SCIDToll-Like Receptor 4Toll-Like Receptor 7Toll-Like Receptor 9Toll-Like ReceptorsTLR7 protein, humanTLR9 protein, humanTlr9 protein, mouseToll-Like Receptor 4Toll-Like Receptor 7Toll-Like Receptor 9Toll-Like ReceptorsChloroquineCholangiocarcinomaCpG-ODNImiquimodIRS-954TLR

Identifiers

PMID33939146
OpenAlexW3158260442

What OpenQuestion holds

Textmetadata
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.