Evidence map›Paper›PMID 40341024›Full record

ArticleJournal for immunotherapy of cancer2025

Blocking LIF and PD-L1 enhances the antitumor efficacy of SBRT in murine PDAC models.

Jian Ye, Shuyang S Qin, Angela L Hughson, Gary Hannon, Noah A Salama, Tara G Vrooman, Maggie L Lesch, Sidney Lesser, Sarah L Eckl, Rachel Jewell and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 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

20 authors.

Jian YeDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.ORCID http://orcid.org/0000-0002-6955-9262
Shuyang S QinDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Angela L HughsonDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Gary HannonDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.ORCID http://orcid.org/0000-0003-1204-0299
Noah A SalamaDepartment of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA.
Tara G VroomanDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Maggie L LeschDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Sidney LesserDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Sarah L EcklDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Rachel JewellDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Lauren BenoodtGenomic Research Center, University of Rochester Medical Center, Rochester, New York, USA.
Bradley N MillsDepartment 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 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.
Laura M CalviWilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, USA.
David LinehanDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA.
Nadia LuheshiThe Discovery Center, Cambridge Biomedical Campus, Cambridge, UK.
Jim EylesOncology R&D, Research and Early Development, AstraZeneca R&D, Cambridge, Cambridgeshire, UK.
Scott A GerberDepartment of Surgery, University of Rochester Medical Center, Rochester, New York, USA scott_gerber@urmc.rochester.edu.

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
University of Rochester Wilmot Cancer Institute Support GrantP30CA272302 · NCI · UNIVERSITY OF ROCHESTER · PI JONATHAN W FRIEDBERG · 2025 to 2026
$6.4M
Modulating innate immune cells in the tumor microenvironment of pancreas cancer to enhance anti-tumor immunityR01CA168863 · NCI · WASHINGTON UNIVERSITY · PI LINEHAN, DAVID C · 2013 to 2023
$3.6M
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 P30 CA272302NCI NIH HHS R01 CA168863NCI NIH HHS R01 CA230277NCI NIH HHS R01 CA236390NCI NIH HHS R01 CA262580NIAID NIH HHS T32 AI007285
6 · The paper itself

Abstract

backgroundRecent preclinical and clinical data suggest that leukemia inhibitory factor (LIF) is a potential target for various tumor types including pancreatic ductal adenocarcinoma as LIF is involved in multiple protumor processes including cancer stem cell maintenance, epithelial-mesenchymal transition (EMT), immunosuppression, and chemo/radioresistance. Anti-LIF antibody therapy has demonstrated safety and tolerability but limited efficacy in phase 1 clinical trial in advanced solid tumors. This prompted us to explore combination therapies, suggesting that LIF blockade, when combined with standard-of-care chemotherapy, radiotherapy, and/or immunotherapy, could present a promising therapeutic strategy.

methodsWe evaluated the impact of combining systemic inhibition of LIF/programmed death-ligand 1 (PD-L1) with localized stereotactic body radiotherapy (SBRT) on tumor progression across multiple murine orthotopic pancreatic tumor models and examined systemic antitumor immunity using a hepatic rechallenge model. The antitumor immune response was characterized throughflow cytometry and Luminex assays. To identify differentially expressed genes and signaling pathways following treatment, we performed bulk RNA sequencing on pancreatic tumors. Additionally, single-cell RNA sequencing was conducted to further examine changes in tumor-infiltrating immune cells and their signaling pathways.

resultsWe showed that simultaneous inhibition of LIF and PD-L1 significantly amplified the antitumor efficacy of SBRT, resulting in extended survival. The triple therapy (SBRT+anti-LIF+anti-PD-L1) generated an immunostimulatory tumor microenvironment, characterized by a proinflammatory shift in the cytokine/chemokine profile, increased infiltration of effector CD8

Indexed as

B7-H1 AntigenCarcinoma, Pancreatic DuctalLeukemia Inhibitory FactorPancreatic NeoplasmsRadiosurgeryAnimalsCell Line, TumorDisease Models, AnimalFemaleHumansMiceB7-H1 AntigenCd274 protein, mouseLeukemia Inhibitory FactorGastrointestinal CancerImmunotherapyRadiotherapy/radioimmunotherapy

Identifiers

PMID40341024
PMCPMC12067785

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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.