Evidence map›Paper›PMID 40815670›Full record

ArticleScience immunology2025

Combined Flt3L and CD40 agonism restores dendritic cell-driven T cell immunity in pancreatic cancer.

Graham D Hogg, Alyssa G Weinstein, Natalie L Kingston, Xiuting Liu, Olivia M Dres, Liang-I Kang, Varintra E Lander, Yu-Lan Kao, Faiz Ahmad, Brett L Knolhoff and 12 more

Abstract read
In one paragraph

Article in Science immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Hypoxia Impairs CD8Cancers · 2026
    Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. 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

22 authors.

Graham D HoggDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0002-7143-0695
Alyssa G WeinsteinDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0001-9342-0263
Natalie L KingstonDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0003-0122-907X
Xiuting LiuDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0003-3791-3885
Olivia M DresDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0003-0310-0958
Liang-I KangDepartment of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0001-7025-3095
Varintra E LanderDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0001-8299-7104
Yu-Lan KaoDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0003-1229-7502
Faiz AhmadDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0002-0450-042X
Brett L KnolhoffDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0002-0115-7355
Varun V ShenoyDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0009-0000-9461-1619
Blake SellsDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0002-4500-1256
Reyka G JayasingheDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0003-2368-4890
Andrew HoustonDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Tiantian LiuDepartment of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0001-9377-9938
John M HerndonDepartment of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0002-8378-9654
Kenneth M MurphyDepartment of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0002-3505-9630
Li DingDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Ryan C FieldsDepartment of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0001-6176-8943
Roheena Z PanniDepartment of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
William G HawkinsDepartment of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.ORCID 0000-0001-7087-3585
David G DeNardoDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0002-3655-5783

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI AIMEE S JAMES · 2001 to 2026
$128.0M
Washington University Paul Calabresi K12 Career Development Award for Clinical OncologyK12CA167540 · NCI · WASHINGTON UNIVERSITY · PI John F. Dipersio, Ramaswamy Govindan · 2012 to 2026
$11.7M
Washington University SPORE in Pancreatic CancerP50CA196510 · NCI · WASHINGTON UNIVERSITY · PI HAWKINS, WILLIAM G · 2016 to 2020
$10.9M
Washington University SPORE in Pancreatic CancerP50CA272213 · NCI · WASHINGTON UNIVERSITY · PI David G DeNardo, WILLIAM G HAWKINS · 2023 to 2026
$10.7M
Washington University (WU) ROBIN Center: MicroEnvironment and Tumor Effects Of Radiotherapy (METEOR)U54CA274318 · NCI · WASHINGTON UNIVERSITY · PI Clifford Grant Robinson, Julie Kristina Schwarz · 2023 to 2026
$7.7M
The Impact of Macrophage Origin on the Pathogenesis and Treatment Resistance of Pancreatic CancerR01CA177670 · NCI · WASHINGTON UNIVERSITY · PI DENARDO, DAVID G · 2014 to 2023
$3.3M
Stomal Senescence Regulator of Tumor Immunity and ProgressionR01CA286615 · NCI · WASHINGTON UNIVERSITY · PI David G DeNardo, Paolo Provenzano · 2024 to 2026
$3.2M
Re-wiring PDAC Tumor Immunity Through Dendritic CellsR01CA262506 · NCI · WASHINGTON UNIVERSITY · PI DENARDO, DAVID G, DESELM, CARL · 2021 to 2025
$2.8M
Targeting Focal Adhesion Kinase to Improve RT-inducted Tumor ImmunityR01CA248917 · NCI · WASHINGTON UNIVERSITY · PI DENARDO, DAVID G, KIM, HYUN · 2020 to 2024
$2.5M
The Impact of Metastatic Site On Dendritic Cell-Driven Tumor ImmunityU01CA284086 · NCI · WASHINGTON UNIVERSITY · PI David G DeNardo, Li Ding · 2023 to 2026
$2.3M
Exploiting Integrin Signaling to Overcome Resistance to ImmunotherapyR01CA244938 · NCI · WASHINGTON UNIVERSITY · PI DENARDO, DAVID G, GUPTA, VINEET · 2020 to 2024
$2.2M
Harnessing Dendritic Cells as a Novel Therapy in Pancreatic Ductal AdenocarcinomaF30CA254087 · NCI · WASHINGTON UNIVERSITY · PI HOGG, GRAHAM DOUGLAS · 2020 to 2023
$168k
NCI NIH HHS F30 CA243233NCI NIH HHS F30 CA254087NCI NIH HHS F30 CA298121NCI NIH HHS K12 CA167540NCI NIH HHS P30 CA091842NCI NIH HHS P50 CA196510NCI NIH HHS P50 CA272213NCI NIH HHS R01 CA177670NCI NIH HHS R01 CA244938NCI NIH HHS R01 CA248917NCI NIH HHS R01 CA262506NCI NIH HHS R01 CA286615NCI NIH HHS U01 CA284086NCI NIH HHS U54 CA274318
6 · The paper itself

Abstract

T cell-directed immunotherapies have largely failed to slow progression of pancreatic ductal adenocarcinoma (PDAC) because of poor tumor antigenicity and an immunosuppressive tumor microenvironment. We hypothesized that conventional dendritic cell (cDC) suppression in PDAC may further impair tumor immunity. We found that low tissue expression of Fms-like tyrosine kinase 3 ligand (Flt3L) partially underlies cDC deficits. Treatment with systemic Flt3L and CD40 agonists restored cDC number and function in murine models and clinical trial samples from patients with PDAC. CD40 agonism alone did not fully activate cDCs; however, when combined with Flt3L, dual therapy triggered a cDC-driven type I immune response characterized by T cell infiltration, interleukin-12 production, and reciprocal interferon-γ (IFN-γ) responses. In mice, cDC1s were responsible for CD8

Indexed as

Carcinoma, Pancreatic DuctalCD40 AntigensDendritic CellsMembrane ProteinsPancreatic NeoplasmsAnimalsCD8-Positive T-LymphocytesCell Line, TumorFemaleHumansMaleMiceMice, Inbred C57BLCD40 Antigensflt3 ligand proteinMembrane Proteins

Identifiers

PMID40815670
PMCPMC13034498

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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.