Evidence map›Paper›PMID 29532035›Full record

ArticleScience advances2018

Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles.

Franz L Ricklefs, Quazim Alayo, Harald Krenzlin, Ahmad B Mahmoud, Maria C Speranza, Hiroshi Nakashima, Josie L Hayes, Kyungheon Lee, Leonora Balaj, Carmela Passaro and 19 more

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

Article in Science advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 396 papers.

0numbers the graph read from it
0cells of the map it votes in
396citing papers in PubMed
25.1field-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

396 citing papers in PubMed, 598 citations in OpenAlex.

  1. Trial
  2. Pembrolizumab in Combination with Neoadjuvant Chemoradiotherapy for Patients with Resectable Adenocarcinoma of the Gastroesophageal Junction.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Trial
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  9. Tumor-intrinsic TLR4 signaling as a context-dependent rheostat in glioblastoma.Journal of molecular medicine (Berlin, Germany) · 2026
    Review
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  12. Article
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  14. Article
  15. Article
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336 more citing papers are in PubMed but not listed here.

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

29 authors at 7 institutions in 3 countries.

Franz L RicklefsHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-1321-6930
Quazim AlayoHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-5524-7105
Harald KrenzlinHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-9001-8006
Ahmad B MahmoudHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Maria C SperanzaHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Hiroshi NakashimaHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Josie L HayesSchool of Public Health, University of California, Berkeley, Berkeley, CA 94720, USA.ORCID 0000-0001-6402-6320
Kyungheon LeeCenter for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Leonora BalajDepartment of Neurosurgery, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0003-0931-9715
Carmela PassaroHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-2401-520X
Arun K RoojHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-3603-6828
Susanne KrasemannInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID 0000-0001-8795-818X
Bob S CarterDepartment of Neurosurgery, Massachusetts General Hospital, Boston, MA 02114, USA.
Clark C ChenDepartment of Neurosurgery, University of California, San Diego, La Jolla, CA 92121, USA.
Tyler SteedDepartment of Neurosurgery, University of California, San Diego, La Jolla, CA 92121, USA.ORCID 0000-0002-8963-0652
Jeffrey TreiberDepartment of Neurosurgery, University of California, San Diego, La Jolla, CA 92121, USA.ORCID 0000-0001-5559-8511
Scott RodigDepartment of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.ORCID 0000-0003-1761-9769
Katherine YangDepartment of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.ORCID 0000-0003-0182-950X
Ichiro NakanoComprehensive Cancer Center, University of Birmingham, Birmingham, AL 35294, USA.
Hakho LeeCenter for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0002-0087-0909
Ralph WeisslederCenter for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0003-0828-4143
Xandra O BreakefieldDepartments of Neurology and Radiology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0001-6036-0399
Jakub GodlewskiHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-2122-9798
Manfred WestphalDepartment of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Katrin LamszusDepartment of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Gordon J FreemanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.ORCID 0000-0002-7210-5616
Agnieszka BroniszHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-5841-1051
Sean E LawlerHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-1633-2339
E Antonio ChioccaHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-5183-1670
Brigham and Women's Hospital · USMassachusetts General Hospital · USUniversität Hamburg · DEUniversity of California San Diego · USHarvard University · USUniversity of Alabama at Birmingham · USUniversity of California, Berkeley · US

Funding

The role of microvesicles in giloma virotherapyP01CA069246 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CARTER, BOB S · 1996 to 2021
$30.9M
Transfer of microRNA regulators from glioblastoma to brain microenvironment U19CA179563 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BREAKEFIELD, XANDRA OWENS, CHAREST, ALAIN · 2013 to 2017
$8.6M
The power of extracellular vesicles in glioblastomaR35CA232103 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BREAKEFIELD, XANDRA OWENS · 2018 to 2024
$6.9M
exRNA Biomarkers for Human GliomaUH3TR000931 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CARTER, BOB S, HOCHBERG, FRED H · 2015 to 2017
$3.0M
MicroRNA128 Regulation of Polycomb Repressor Complexes1 and 2 in GlioblastomaR01CA176203 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI GODLEWSKI, JAKUB · 2014 to 2018
$1.8M
Targeting Mechanisms of Acquired Temozolomide Resistance in GlioblastomaR01NS097649 · NINDS · UNIVERSITY OF MINNESOTA · PI CHEN, CLARK CHIN-CHUNG · 2016 to 2021
$1.7M
NCATS NIH HHS UH3 TR000931NCI NIH HHS P01 CA069246NCI NIH HHS R01 CA176203NCI NIH HHS R35 CA232103NCI NIH HHS U19 CA179563NINDS NIH HHS R01 NS097649
6 · The paper itself

Abstract

Binding of programmed death ligand-1 (PD-L1) to programmed cell death protein-1 (PD1) leads to cancer immune evasion via inhibition of T cell function. One of the defining characteristics of glioblastoma, a universally fatal brain cancer, is its profound local and systemic immunosuppression. Glioblastoma has also been shown to generate extracellular vesicles (EVs), which may play an important role in tumor progression. We thus hypothesized that glioblastoma EVs may be important mediators of immunosuppression and that PD-L1 could play a role. We show that glioblastoma EVs block T cell activation and proliferation in response to T cell receptor stimulation. PD-L1 was expressed on the surface of some, but not of all, glioblastoma-derived EVs, with the potential to directly bind to PD1. An anti-PD1 receptor blocking antibody significantly reversed the EV-mediated blockade of T cell activation but only when PD-L1 was present on EVs. When glioblastoma PD-L1 was up-regulated by IFN-γ, EVs also showed some PD-L1-dependent inhibition of T cell activation. PD-L1 expression correlated with the mesenchymal transcriptome profile and was anatomically localized in the perinecrotic and pseudopalisading niche of human glioblastoma specimens. PD-L1 DNA was present in circulating EVs from glioblastoma patients where it correlated with tumor volumes of up to 60 cm

Indexed as

Immune EvasionAntigens, NeoplasmB7-H1 AntigenBrain NeoplasmsCell Line, TumorExtracellular VesiclesGene Expression Regulation, NeoplasticGlioblastomaHumansInterferon-gammaLymphocyte ActivationNeoplastic Stem CellsReceptors, Antigen, T-CellT-LymphocytesUp-RegulationAntigens, NeoplasmB7-H1 AntigenCD274 protein, humanInterferon-gammaReceptors, Antigen, T-Cell

Identifiers

PMID29532035
PMCPMC5842038
OpenAlexW2793992337

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Read underepoch 390

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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.