Evidence map›Paper›PMID 37263309›Full record

ArticleGastroenterology2023

Transforming Growth Factor-β Blockade in Pancreatic Cancer Enhances Sensitivity to Combination Chemotherapy.

Li Qiang, Megan T Hoffman, Lestat R Ali, Jaime I Castillo, Lauren Kageler, Ayantu Temesgen, Patrick Lenehan, S Jennifer Wang, Elisa Bello, Victoire Cardot-Ruffino and 8 more

Open access · greenAbstract read
In one paragraph

Article in Gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
13.8field-weighted citation impact, top 1% 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

49 citing papers in PubMed, 60 citations in OpenAlex.

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  15. Recent advances in biomarkers for cardiac fibrosis.Frontiers in cardiovascular medicine · 2026
    Review
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  17. Pancreatic cancer-associated myofibroblasts: a review.International journal of biological sciences · 2026
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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

18 authors at 6 institutions in 1 country.

Li QiangDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Immunology, Harvard Medical School, Boston, Massachusetts.
Megan T HoffmanDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Immunology, Harvard Medical School, Boston, Massachusetts.
Lestat R AliDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts; Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Jaime I CastilloDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Lauren KagelerDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Immunology, Harvard Medical School, Boston, Massachusetts.
Ayantu TemesgenDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Immunology, Harvard Medical School, Boston, Massachusetts.
Patrick LenehanDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Immunology, Harvard Medical School, Boston, Massachusetts.
S Jennifer WangDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Elisa BelloDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts; Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Victoire Cardot-RuffinoDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Immunology, Harvard Medical School, Boston, Massachusetts.
Giselle A UribeDepartment of Medicine, Harvard Medical School, Boston, Massachusetts; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Annan YangDepartment of Medicine, Harvard Medical School, Boston, Massachusetts; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Michael DouganDivision of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Andrew J AguirreDepartment of Medicine, Harvard Medical School, Boston, Massachusetts; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Srivatsan RaghavanDepartment of Medicine, Harvard Medical School, Boston, Massachusetts; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Marc PelletierNovartis Institute for Biomedical Research, Cambridge, Massachusetts.
Viviana CremascoNovartis Institute for Biomedical Research, Cambridge, Massachusetts.
Stephanie K DouganDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Immunology, Harvard Medical School, Boston, Massachusetts. Electronic address: stephanie_dougan@dfci.harvard.edu.
Dana-Farber Cancer Institute · USHarvard University · USMassachusetts General Hospital · USBroad Institute · USBoston Biomedical Research Institute · USNovartis (United States) · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
Stromal modulation of pancreatic cancer malignant cell state and therapeutic sensitivityU01CA274276 · NCI · DANA-FARBER CANCER INST · PI Andrew James Aguirre, Stephanie Dougan · 2022 to 2026
$5.1M
Strategies for Receptor inhibition in immunotherapyR01CA177684 · NCI · STANFORD UNIVERSITY · PI DOUGAN, MICHAEL LAWRENCE, GARCIA, KENAN CHRISTOPHER · 2014 to 2025
$3.5M
Systematic interrogation of the pancreatic cancer microenvironment in patient-derived specimensU01CA224146 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2017 to 2021
$3.0M
Cancer Immunology Training GrantT32CA207021 · NCI · DANA-FARBER CANCER INST · PI WUCHERPFENNIG, KAI W · 2016 to 2020
$2.4M
CDK4/6 inhibition during CD8 T cell priming potentiates memory formation in mice and humansR01AI158488 · NIAID · DANA-FARBER CANCER INST · PI DOUGAN, STEPHANIE · 2021 to 2025
$2.2M
Mechanisms of response and resistance to KRAS inhibition in pancreatic cancerR01CA276268 · NCI · DANA-FARBER CANCER INST · PI Andrew James Aguirre · 2023 to 2026
$2.2M
Regulation of brown fat metabolism by the immune receptor PD-L1K08DK114563 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI DOUGAN, MICHAEL LAWRENCE · 2017 to 2021
$868k
NCI NIH HHS R01 CA177684NCI NIH HHS R01 CA276268NCI NIH HHS T32 CA207021NCI NIH HHS U01 CA224146NCI NIH HHS U01 CA274276NIAID NIH HHS R01 AI158488NIDDK NIH HHS K08 DK114563NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM144273
6 · The paper itself

Abstract

BACKGROUND &

aimsTransforming growth factor-b (TGFb) plays pleiotropic roles in pancreatic cancer, including promoting metastasis, attenuating CD8 T-cell activation, and enhancing myofibroblast differentiation and deposition of extracellular matrix. However, single-agent TGFb inhibition has shown limited efficacy against pancreatic cancer in mice or humans.

methodsWe evaluated the TGFβ-blocking antibody NIS793 in combination with gemcitabine/nanoparticle (albumin-bound)-paclitaxel or FOLFIRINOX (folinic acid [FOL], 5-fluorouracil [F], irinotecan [IRI] and oxaliplatin [OX]) in orthotopic pancreatic cancer models. Single-cell RNA sequencing and immunofluorescence were used to evaluate changes in tumor cell state and the tumor microenvironment.

resultsBlockade of TGFβ with chemotherapy reduced tumor burden in poorly immunogenic pancreatic cancer, without affecting the metastatic rate of cancer cells. Efficacy of combination therapy was not dependent on CD8 T cells, because response to TGFβ blockade was preserved in CD8-depleted or recombination activating gene 2 (RAG2

conclusionsTGFβ regulates pancreatic cancer cell plasticity between classical and basal cell states. TGFβ blockade in orthotropic models of pancreatic cancer enhances sensitivity to chemotherapy by promoting a classical malignant cell state. This study provides scientific rationale for evaluation of NIS793 with FOLFIRINOX or gemcitabine/nanoparticle (albumin-bound) paclitaxel chemotherapy backbone in the clinical setting and supports the concept of manipulating cancer cell plasticity to increase the efficacy of combination therapy regimens.

Indexed as

Antineoplastic AgentsPancreatic NeoplasmsAlbuminsAnimalsAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsGemcitabineHumansMicePaclitaxelTransforming Growth Factor betaTransforming Growth FactorsTumor MicroenvironmentAlbuminsAntibodies, MonoclonalAntineoplastic AgentsGemcitabineNIS-793PaclitaxelTransforming Growth Factor betaTransforming Growth FactorsChemotherapyImmunotherapyPancreatic cancerTGF-βTumor microenvironment

Identifiers

PMID37263309
PMCPMC10526623
OpenAlexW4379095278

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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.