Evidence map›Paper›PMID 39188754›Full record

ArticleOncoimmunology2024

Local therapy with combination TLR agonists stimulates systemic anti-tumor immunity and sensitizes tumors to immune checkpoint blockade.

Francois Xavier Rwandamuriye, Tao Wang, Hanfu Zhang, Omar Elaskalani, Jorren Kuster, Xueting Ye, Breana Vitali, Juliët Schreurs, M Lizeth Orozco Morales, Marck Norret and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncoimmunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. 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

15 authors.

Francois Xavier RwandamuriyeTelethon Kids Institute, University of Western Australia, Nedlands, WA, Australia.
Tao WangTelethon Kids Institute, University of Western Australia, Nedlands, WA, Australia.
Hanfu ZhangSchool of Molecular Sciences, University of Western Australia, Crawley, WA, Australia.
Omar ElaskalaniTelethon Kids Institute, University of Western Australia, Nedlands, WA, Australia.
Jorren KusterTelethon Kids Institute, University of Western Australia, Nedlands, WA, Australia.
Xueting YeTelethon Kids Institute, University of Western Australia, Nedlands, WA, Australia.
Breana VitaliTelethon Kids Institute, University of Western Australia, Nedlands, WA, Australia.
Juliët SchreursTelethon Kids Institute, University of Western Australia, Nedlands, WA, Australia.
M Lizeth Orozco MoralesTelethon Kids Institute, University of Western Australia, Nedlands, WA, Australia.
Marck NorretSchool of Molecular Sciences, University of Western Australia, Crawley, WA, Australia.
Cameron W EvansSchool of Molecular Sciences, University of Western Australia, Crawley, WA, Australia.
Rachael M ZemekTelethon Kids Institute, University of Western Australia, Nedlands, WA, Australia.
K Swaminathan IyerSchool of Molecular Sciences, University of Western Australia, Crawley, WA, Australia.
W Joost LesterhuisTelethon Kids Institute, University of Western Australia, Nedlands, WA, Australia.
Ben WylieTelethon Kids Institute, University of Western Australia, Nedlands, WA, Australia.ORCID 0000-0001-8781-8611

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Toll-like receptor (TLR) agonists are being developed as anti-cancer therapeutics due to their potent immunostimulatory properties. However, clinical trials testing TLR agonists as monotherapy have often failed to demonstrate significant improvement over standard of care. We hypothesized that the anti-cancer efficacy of TLR agonist immunotherapy could be improved by combinatorial approaches. To prevent increased toxicity, often seen with systemic combination therapies, we developed a hydrogel to deliver TLR agonist combinations at low doses, locally, during cancer debulking surgery. Using tumor models of WEHI 164 and bilateral M3-9-M sarcoma and CT26 colon carcinoma, we assessed the efficacy of pairwise combinations of poly(I:C), R848, and CpG in controlling local and distant tumor growth. We show that combination of the TLR3 agonist poly(I:C) and TLR7/8 agonist R848 drives anti-tumor immunity against local and distant tumors. In addition, combination of local poly(I:C) and R848 sensitized tumors to systemic immune checkpoint blockade, improving tumor control. Mechanistically, we demonstrate that local therapy with poly(I:C) and R848 recruits inflammatory monocytes to the tumor draining lymph nodes early in the anti-tumor response. Finally, we provide proof of concept for intraoperative delivery of poly(I:C) and R848 together via a surgically applicable biodegradable hydrogel.

Indexed as

ImidazolesImmune Checkpoint InhibitorsPoly I-CAnimalsCell Line, TumorColonic NeoplasmsFemaleHumansHydrogelsImmunotherapyMiceMice, Inbred C57BLToll-Like Receptor AgonistsToll-Like ReceptorsHydrogelsImidazolesImmune Checkpoint InhibitorsPoly I-CresiquimodToll-Like Receptor AgonistsToll-Like ReceptorsCancer immunotherapycombination therapyhydrogelinnate immunitysurgeryTLR agonists

Identifiers

PMID39188754
PMCPMC11346538

What OpenQuestion holds

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LicenceCC BY-NC
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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.