Evidence map›Paper›PMID 28115578›Full record

ArticleNeuro-oncology2017

Immunosuppressive tumor-infiltrating myeloid cells mediate adaptive immune resistance via a PD-1/PD-L1 mechanism in glioblastoma.

Joseph P Antonios, Horacio Soto, Richard G Everson, Diana Moughon, Joey R Orpilla, Namjo P Shin, Shaina Sedighim, Janet Treger, Sylvia Odesa, Alexander Tucker and 5 more

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

Article in Neuro-oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers.

0numbers the graph read from it
0cells of the map it votes in
151citing papers in PubMed
8.5field-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

151 citing papers in PubMed, 203 citations in OpenAlex.

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  18. Radioresistance Mechanisms in Head and Neck Cancer.Clinical and experimental otorhinolaryngology · 2025
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91 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

15 authors at 1 institution in 1 country.

Joseph P AntoniosDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Horacio SotoDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Richard G EversonDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Diana MoughonDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Joey R OrpillaDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Namjo P ShinDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Shaina SedighimDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Janet TregerDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Sylvia OdesaDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Alexander TuckerDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
William H YongDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Gang LiDepartment of Biostatistics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Timothy F CloughesyBrain Research Institute, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Linda M LiauDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Robert M PrinsDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
University of California, Los Angeles · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANTON, PETER A · 1991 to 2018
$39.9M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI David A. Nathanson · 2017 to 2026
$25.2M
Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
UCLA Neurosurgery Research Training and Education ProgramR25NS079198 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LIAU, LINDA M · 2012 to 2021
$1.2M
Immunotherapeutic targeting of the Glioblastoma MutanomeR21CA186004 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LARGAESPADA, DAVID ANDREW, PRINS, ROBERT M · 2015 to 2016
$380k
NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA211015NCI NIH HHS R21 CA186004NIAID NIH HHS P30 AI028697NIDDK NIH HHS P30 DK041301NINDS NIH HHS R25 NS079198
6 · The paper itself

Abstract

Background: Adaptive immune resistance in the tumor microenvironment appears to attenuate the immunotherapeutic targeting of glioblastoma (GBM). In this study, we identified a tumor-infiltrating myeloid cell (TIM) population that expands in response to dendritic cell (DC) vaccine treatment. The aim of this study was to understand how this programmed death ligand 1 (PD-L1)-expressing population restricts activation and tumor-cytolytic function of vaccine-induced tumor-infiltrating lymphocytes (TILs). Methods: To test this hypothesis in our in vivo preclinical model, we treated mice bearing intracranial gliomas with DC vaccination ± murine anti-PD-1 monoclonal antibody (mAb) blockade or a colony stimulating factor 1 receptor inhibitor (CSF-1Ri) (PLX3397) and measured overall survival. We then harvested and characterized the PD-L1+ TIM population and its role in TIL activation and tumor cytolysis in vitro. Results: Our data indicated that the majority of PD-L1 expression in the GBM environment is contributed by TIMs rather than by tumor cells themselves. While PD-1 blockade partially reversed the TIL dysfunction, targeting TIMs directly with CSF-1Ri altered TIM expression of key chemotactic factors associated with promoting increased TIL infiltration after vaccination. Neither PD-1 mAb nor CSF-1Ri had a demonstrable therapeutic benefit alone, but when combined with DC vaccination, a significant survival benefit was observed. When the tripartite regimen was given (DC vaccine, PD-1 mAb, PLX3397), long-term survival was noted together with an increase in the number of TILs and TIL activation. Conclusion: Together, these studies elucidate the role that TIMs play in mediating adaptive immune resistance in the GBM microenvironment and provide evidence that they can be manipulated pharmacologically with agents that are clinically available. Development of immune resistance in response to active vaccination in GBM can be reversed with dual administration of CSF-1Ri and PD-1 mAb.

Indexed as

AnimalsAntibodies, MonoclonalB7-H1 AntigenCancer VaccinesFemaleGlioblastomaHumansLymphocytes, Tumor-InfiltratingMiceMice, Inbred C57BLMyeloid CellsProgrammed Cell Death 1 ReceptorReceptor, Macrophage Colony-Stimulating FactorTumor Cells, CulturedTumor MicroenvironmentXenograft Model Antitumor AssaysAntibodies, MonoclonalB7-H1 AntigenCancer VaccinesCD274 protein, humanPDCD1 protein, humanProgrammed Cell Death 1 ReceptorReceptor, Macrophage Colony-Stimulating Factorcancercheckpoint inhibitorsCSF-1Rdendritic cell vaccineglioblastomaimmunotherapyPD-1

Identifiers

PMID28115578
PMCPMC5464463
OpenAlexW2581747126

What OpenQuestion holds

Textmetadata
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.