Evidence map›Paper›PMID 35851308›Full record

ArticleJournal for immunotherapy of cancer2022

Toll-like receptor 7/8 agonist R848 alters the immune tumor microenvironment and enhances SBRT-induced antitumor efficacy in murine models of pancreatic cancer.

Jian Ye, Bradley N Mills, Shuyang S Qin, Jesse Garrett-Larsen, Joseph D Murphy, Taylor P Uccello, Booyeon J Han, Tara G Vrooman, Carl J Johnston, Edith M Lord and 3 more

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

Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 3 pooled it
5.5field-weighted citation impact, top 3% 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

53 citing papers in PubMed, 3 syntheses or guidelines pooled it, 72 citations in OpenAlex.

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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

13 authors at 1 institution in 1 country.

Jian YeDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.ORCID 0000-0002-6955-9262
Bradley N MillsDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Shuyang S QinDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Jesse Garrett-LarsenDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Joseph D MurphyDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Taylor P UccelloDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Booyeon J HanDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Tara G VroomanDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Carl J JohnstonWilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, USA.
Edith M LordCenter for Tumor Immunology Research, University of Rochester Medical Center, Rochester, New York, USA.
Brian A BeltDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
David C LinehanDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Scott A GerberDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA scott_gerber@urmc.rochester.edu.
University of Rochester Medical Center · US

Funding

The T32 Predoctoral Training Program in Immunology (PTPI)T32AI007285 · NIAID · UNIVERSITY OF ROCHESTER · PI Scott Andrew Gerber, JACQUES Robert · 1986 to 2026
$7.6M
Targeting adrenergic stress pathways to Increase tumor sensitivity to radiation and promote development of an anti-tumor immune responseR01CA236390 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI GERBER, SCOTT ANDREW, REPASKY, ELIZABETH A · 2019 to 2023
$2.8M
Development of a New Strategy to Treat Locally Advanced Pancreatic CancerR01CA230277 · NCI · UNIVERSITY OF ROCHESTER · PI GERBER, SCOTT ANDREW · 2019 to 2023
$2.0M
Repolarizing the Tumor and Metastatic Microenvironments to Treat Patients with Pancreatic CancerR01CA262580 · NCI · UNIVERSITY OF ROCHESTER · PI GERBER, SCOTT ANDREW, LINEHAN, DAVID C · 2021 to 2025
$1.6M
NCI NIH HHS R01 CA230277NCI NIH HHS R01 CA236390NCI NIH HHS R01 CA262580NIAID NIH HHS T32 AI007285
6 · The paper itself

Abstract

backgroundStereotactic body radiotherapy (SBRT) has been increasingly used as adjuvant therapy in pancreatic ductal adenocarcinoma (PDAC), and induces immunogenic cell death, which leads to the release of tumor antigen and damage-associated molecular patterns. However, this induction often fails to generate sufficient response to overcome pre-existing tumor microenvironment (TME) immunosuppression. Toll-like receptor (TLR) 7/8 ligands, such as R848, can amplify the effect of tumor vaccines, with recent evidence showing its antitumor effect in pancreatic cancer by modulating the immunosuppressive TME. Therefore, we hypothesized that the combination of R848 and SBRT would improve local and systemic antitumor immune responses by potentiating the antitumor effects of SBRT and reversing the immunosuppressive nature of the PDAC TME.

methodsUsing murine models of orthotopic PDAC, we assessed the combination of intravenous TLR7/8 agonist R848 and local SBRT on tumor growth and immune response in primary pancreatic tumors. Additionally, we employed a hepatic metastatic model to investigate if the combination of SBRT targeting only the primary pancreatic tumor and systemic R848 is effective in controlling established liver metastases.

resultsWe demonstrated that intravenous administration of the TLR7/8 agonist R848, in combination with local SBRT, leads to superior tumor control compared with either treatment alone. The combination of R848 and SBRT results in significant immune activation of the pancreatic TME, including increased tumor antigen-specific CD8

conclusionsThese findings suggest that systemic administration of TLR7/8 agonists in combination with SBRT may be a promising avenue for metastatic PDAC treatment.

Indexed as

Carcinoma, Pancreatic DuctalLiver NeoplasmsPancreatic NeoplasmsRadiosurgeryAdjuvants, ImmunologicAnimalsAntigens, NeoplasmCD8-Positive T-LymphocytesDisease Models, AnimalHumansImidazolesMiceToll-Like Receptor 7Toll-Like Receptor 8Tumor MicroenvironmentAdjuvants, ImmunologicAntigens, NeoplasmImidazolesresiquimodToll-Like Receptor 7Toll-Like Receptor 8Combined Modality TherapyGastrointestinal NeoplasmsImmunotherapyRadiotherapyTumor Microenvironment

Identifiers

PMID35851308
PMCPMC9295644
OpenAlexW4285735812

What OpenQuestion holds

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LicenceCC BY-NC
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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.