Evidence map›Paper›PMID 30824583›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019

Glioblastoma-Derived IL6 Induces Immunosuppressive Peripheral Myeloid Cell PD-L1 and Promotes Tumor Growth.

Jonathan B Lamano, Jason Balquidera Lamano, Yuping D Li, Joseph D DiDomenico, Winward Choy, Dorina Veliceasa, Daniel E Oyon, Shayan Fakurnejad, Leonel Ampie, Kartik Kesavabhotla and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
141citing papers in PubMed, 2 pooled it
10.1field-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

141 citing papers in PubMed, 2 syntheses or guidelines pooled it, 213 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Transcriptomic Correlates of Tumor Cell PD-L1 Expression and Response to Nivolumab Monotherapy in Metastatic Clear Cell Renal Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Trial
  5. Oncoimmunology · 2026
    Article
  6. Article
  7. Crosslink Between Neuroinflammation and Oxidative/Nitrosative Status in the Glioblastoma Tumor Microenvironment: Prognostic and Theranostic Impact.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026
    Article
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  16. Targeted lungScience advances · 2026
    Article
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81 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

18 authors at 5 institutions in 2 countries.

Jonathan B LamanoDepartment of Neurological Surgery, Northwestern University, Chicago, Illinois.
Jason Balquidera LamanoDepartment of Neurological Surgery, Northwestern University, Chicago, Illinois.
Yuping D LiDepartment of Neurological Surgery, Northwestern University, Chicago, Illinois.
Joseph D DiDomenicoDepartment of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona.
Winward ChoyDepartment of Neurological Surgery, University of California San Francisco, San Francisco, California.
Dorina VeliceasaDepartment of Neurological Surgery, Northwestern University, Chicago, Illinois.
Daniel E OyonDepartment of Neurological Surgery, Northwestern University, Chicago, Illinois.
Shayan FakurnejadStanford School of Medicine, Stanford University, Stanford, California.
Leonel AmpieDepartment of Neurosurgery, University of Virginia School of Medicine, University of Virginia, Charlottesville, Virginia.
Kartik KesavabhotlaDepartment of Neurological Surgery, Northwestern University, Chicago, Illinois.
Rajwant KaurDepartment of Neurological Surgery, Northwestern University, Chicago, Illinois.
Gurvinder KaurDepartment of Neurological Surgery, Northwestern University, Chicago, Illinois.
Dauren BiyashevDepartment of Neurological Surgery, Northwestern University, Chicago, Illinois.
Dusten J UnruhDepartment of Neurological Surgery, Northwestern University, Chicago, Illinois.
Craig M HorbinskiDepartment of Neurological Surgery, Northwestern University, Chicago, Illinois.
C David JamesDepartment of Neurological Surgery, Northwestern University, Chicago, Illinois.
Andrew T Parsa
Orin BlochDepartment of Neurological Surgery, Northwestern University, Chicago, Illinois. orin.bloch@northwestern.edu.
Northwestern University · USBarrow Neurological Institute · USNational Institute of Neurological Disorders and Stroke · USStanford Medicine · USUniversity of California, San Francisco · US

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9M
Northwestern University Clinical and Translational Science Institute (NUCATS)UL1TR001422 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI D'AQUILA, RICHARD · 2015 to 2023
$56.8M
STINGing GBM: A First-in- Man Clinical Trial in Surgical Resectable Recurrent GBMP50CA221747 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Pouya Jamshidi · 2018 to 2026
$21.4M
TRAINING PROGRAM IN SIGNAL TRANSDUCTION AND CANCERT32CA070085 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LEONIDAS C. PLATANIAS · 1997 to 2026
$5.7M
Tissue Factor as a Key Determinant of IDH1 Mutant versus IDH1 Wild-type Glioma Thrombosis and MalignancyR01NS102669 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI HORBINSKI, CRAIG MICHAEL · 2017 to 2021
$1.7M
Radiation + Temozolomide Induced Mutation and Malignant Progression of GBMR01NS095642 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI JAMES, CHARLES DAVID · 2016 to 2020
$1.6M
B7H1 Mediated Immunosuppression in GliomaR01CA164714 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI BLOCH, ORIN · 2013 to 2018
$1.6M
The Significance of Isocitrate Dehydrogenase Mutations in GliomasK08CA155764 · NCI · UNIVERSITY OF KENTUCKY · PI HORBINSKI, CRAIG MICHAEL · 2011 to 2015
$857k
B7-H1 Expressing Macrophages Mediate Immunosupression in GliomaR00NS078055 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BLOCH, ORIN · 2014 to 2016
$747k
B7-H1 Expressing Macrophages Mediate Immunosupression in GliomaK99NS078055 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BLOCH, ORIN · 2012 to 2013
$279k
The role of glioblastoma derived activated leukocyte cell adhesion molecule in peripheral monocyte PD-L1 induction and immunosuppressionF30CA206413 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LAMANO, JONATHAN BALQUIEDRA · 2016 to 2019
$197k
Tissue Factor/Protease-Activated Receptor 2 in IDH1 wild-type and IDH1 mutant gliomasF32CA216996 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI UNRUH, DUSTEN · 2018 to 2020
$192k
Howard Hughes Medical InstituteNCATS NIH HHS UL1 TR001422NCI NIH HHS F30 CA206413NCI NIH HHS F32 CA216996NCI NIH HHS K08 CA155764NCI NIH HHS P30 CA060553NCI NIH HHS P50 CA221747NCI NIH HHS R01 CA164714NCI NIH HHS T32 CA070085NINDS NIH HHS F32 NS101884NINDS NIH HHS K99 NS078055NINDS NIH HHS R00 NS078055NINDS NIH HHS R01 NS095642NINDS NIH HHS R01 NS102669
6 · The paper itself

Abstract

purposeUpregulation of programmed death-ligand 1 (PD-L1) on circulating and tumor-infiltrating myeloid cells is a critical component of GBM-mediated immunosuppression that has been associated with diminished response to vaccine immunotherapy and poor survival. Although GBM-derived soluble factors have been implicated in myeloid PD-L1 expression, the identity of such factors has remained unknown. This study aimed to identify factors responsible for myeloid PD-L1 upregulation as potential targets for immune modulation. EXPERIMENTAL

designConditioned media from patient-derived GBM explant cell cultures was assessed for cytokine expression and utilized to stimulate naïve myeloid cells. Myeloid PD-L1 induction was quantified by flow cytometry. Candidate cytokines correlated with PD-L1 induction were evaluated in tumor sections and plasma for relationships with survival and myeloid PD-L1 expression. The role of identified cytokines on immunosuppression and survival was investigated

resultsGBM-derived IL6 was identified as a cytokine that is necessary and sufficient for myeloid PD-L1 induction in GBM through a STAT3-dependent mechanism. Inhibition of IL6 signaling in orthotopic murine glioma models was associated with reduced myeloid PD-L1 expression, diminished tumor growth, and increased survival. The therapeutic benefit of anti-IL6 therapy proved to be CD8

conclusionsOur findings suggest that disruption of IL6 signaling in GBM reduces local and systemic myeloid-driven immunosuppression and enhances immune-mediated antitumor responses against GBM.

Indexed as

AnimalsB7-H1 AntigenBrain NeoplasmsCell ProliferationGlioblastomaHumansImmunosuppression TherapyInterleukin-6MiceMice, Inbred C57BLMyeloid CellsPrognosisSurvival RateTumor Cells, CulturedTumor MicroenvironmentB7-H1 AntigenCD274 protein, humanCd274 protein, mouseIL6 protein, humanInterleukin-6

Identifiers

PMID30824583
PMCPMC6571046
OpenAlexW2919041616

What OpenQuestion holds

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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.