Evidence map›Paper›PMID 28404866›Full record

ArticleScience translational medicine2017

Combined antiangiogenic and anti-PD-L1 therapy stimulates tumor immunity through HEV formation.

Elizabeth Allen, Arnaud Jabouille, Lee B Rivera, Inge Lodewijckx, Rindert Missiaen, Veronica Steri, Kevin Feyen, Jaime Tawney, Douglas Hanahan, Iacovos P Michael and 1 more

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

Article in Science translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 515 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
515citing papers in PubMed, 4 pooled it
26.6field-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

515 citing papers in PubMed, 4 syntheses or guidelines pooled it, 771 citations in OpenAlex.

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455 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 3 countries.

Elizabeth AllenLaboratory of Tumor Microenvironment and Therapeutic Resistance, VIB-Center for Cancer Biology, Department of Oncology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.ORCID 0000-0002-5379-2668
Arnaud JabouilleBrain Tumor Research Center, Department of Neurological Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0002-2281-430X
Lee B RiveraBrain Tumor Research Center, Department of Neurological Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0003-2658-1862
Inge LodewijckxLaboratory of Tumor Microenvironment and Therapeutic Resistance, VIB-Center for Cancer Biology, Department of Oncology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
Rindert MissiaenLaboratory of Tumor Microenvironment and Therapeutic Resistance, VIB-Center for Cancer Biology, Department of Oncology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.ORCID 0000-0002-8192-0567
Veronica SteriBrain Tumor Research Center, Department of Neurological Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Kevin FeyenLaboratory of Tumor Microenvironment and Therapeutic Resistance, VIB-Center for Cancer Biology, Department of Oncology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
Jaime TawneyBrain Tumor Research Center, Department of Neurological Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Douglas HanahanSwiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Station 19, 1015 Lausanne, Switzerland.
Iacovos P MichaelSwiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Station 19, 1015 Lausanne, Switzerland.ORCID 0000-0001-7674-1233
Gabriele BergersLaboratory of Tumor Microenvironment and Therapeutic Resistance, VIB-Center for Cancer Biology, Department of Oncology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium. gabriele.bergers@kuleuven.vib.be.ORCID 0000-0003-3545-5171
University of California, San Francisco · USVIB-KU Leuven Center for Cancer Biology · BEÉcole Polytechnique Fédérale de Lausanne · CH

Funding

The vascular niche in glioma propagation and resistance to therapyU54CA163155 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LAKINS, JOHNATHON NEIL · 2011 to 2015
$4.4M
Autophagy as a microenvironmental regulator of tumorigenesis and resistanceR01CA188404 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BERGERS, GABRIELE, DEBNATH, JAYANTA · 2014 to 2018
$2.1M
Inter-regulatory function of immune-modulation and angiogenesis in cancerR01CA201537 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BERGERS, GABRIELE · 2016 to 2020
$1.7M
NCI NIH HHS R01 CA188404NCI NIH HHS R01 CA201537NCI NIH HHS U54 CA163155
6 · The paper itself

Abstract

Inhibitors of VEGF (vascular endothelial growth factor)/VEGFR2 (vascular endothelial growth factor receptor 2) are commonly used in the clinic, but their beneficial effects are only observed in a subset of patients and limited by induction of diverse relapse mechanisms. We describe the up-regulation of an adaptive immunosuppressive pathway during antiangiogenic therapy, by which PD-L1 (programmed cell death ligand 1), the ligand of the negative immune checkpoint regulator PD-1 (programmed cell death protein 1), is enhanced by interferon-γ-expressing T cells in distinct intratumoral cell types in refractory pancreatic, breast, and brain tumor mouse models. Successful treatment with a combination of anti-VEGFR2 and anti-PD-L1 antibodies induced high endothelial venules (HEVs) in PyMT (polyoma middle T oncoprotein) breast cancer and RT2-PNET (Rip1-Tag2 pancreatic neuroendocrine tumors), but not in glioblastoma (GBM). These HEVs promoted lymphocyte infiltration and activity through activation of lymphotoxin β receptor (LTβR) signaling. Further activation of LTβR signaling in tumor vessels using an agonistic antibody enhanced HEV formation, immunity, and subsequent apoptosis and necrosis in pancreatic and mammary tumors. Finally, LTβR agonists induced HEVs in recalcitrant GBM, enhanced cytotoxic T cell (CTL) activity, and thereby sensitized tumors to antiangiogenic/anti-PD-L1 therapy. Together, our preclinical studies provide evidence that anti-PD-L1 therapy can sensitize tumors to antiangiogenic therapy and prolong its efficacy, and conversely, antiangiogenic therapy can improve anti-PD-L1 treatment specifically when it generates intratumoral HEVs that facilitate enhanced CTL infiltration, activity, and tumor cell destruction.

Indexed as

Angiogenesis InhibitorsAnimalsBreast NeoplasmsFemaleInterferon-gammaMiceMice, Inbred C57BLNeoplasm Recurrence, LocalPancreatic NeoplasmsProgrammed Cell Death 1 ReceptorSignal TransductionT-Lymphocytes, CytotoxicVascular Endothelial Growth Factor AAngiogenesis InhibitorsInterferon-gammaProgrammed Cell Death 1 ReceptorVascular Endothelial Growth Factor A

Identifiers

PMID28404866
PMCPMC5554432
OpenAlexW2605792367

What OpenQuestion holds

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Read underepoch 390

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.