Evidence map›Paper›PMID 34836966›Full record

Observational studyNature communications2021

Neoadjuvant PD-1 blockade induces T cell and cDC1 activation but fails to overcome the immunosuppressive tumor associated macrophages in recurrent glioblastoma.

Alexander H Lee, Lu Sun, Aaron Y Mochizuki, Jeremy G Reynoso, Joey Orpilla, Frances Chow, Jenny C Kienzler, Richard G Everson, David A Nathanson, Steven J Bensinger and 4 more

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

Observational study in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
174citing papers in PubMed, 1 pooled it
15.9field-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

174 citing papers in PubMed, 1 synthesis or guideline pooled it, 250 citations in OpenAlex.

  1. Pooled it
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  6. Degradation fragments of Tau and type IV collagen as serum biomarkers in patients with recurrent glioblastoma treated with nivolumab and bevacizumab.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Trial
  7. Trial
  8. Review
  9. Mechanisms, Microenvironments, and Models: Understanding Therapeutic Resistance in Glioblastoma.International journal of radiation oncology, biology, physics · 2026
    Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Immune Subtypes and Survival in Patients with Primary Glioma.medRxiv : the preprint server for health sciences · 2026
    Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review

114 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

14 authors at 1 institution in 1 country.

Alexander H Lee *Department of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0002-4583-0740
Lu Sun *Department of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Aaron Y MochizukiDepartment of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0003-1073-916X
Jeremy G ReynosoDepartment of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0002-4376-0101
Joey OrpillaDepartment of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0002-6679-9463
Frances ChowDepartment of Neurology/Neuro-Oncology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0001-5402-2473
Jenny C KienzlerDepartment of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0003-2480-0451
Richard G EversonDepartment of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0003-2809-3061
David A NathansonDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Steven J BensingerDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0002-9657-4206
Linda M LiauDepartment of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0002-4053-0052
Timothy CloughesyDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0002-8656-7483
Willy HugoUCLA Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, 90095, USA. HWilly@mednet.ucla.edu.
Robert M PrinsDepartment of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, 90095, USA. RPrins@mednet.ucla.edu.ORCID http://orcid.org/0000-0002-6282-6583
University of California, Los Angeles · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert Damoiseaux · 1985 to 2026
$134.5M
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
UCLA Tumor Immunology Training ProgramT32CA009120 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Steven M. Dubinett, MICHAEL A TEITELL · 1985 to 2026
$10.3M
Mammalian models for integrated metabolic and molecular profiling of malignant gliomaR01CA227089 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GRAEBER, THOMAS G, NATHANSON, DAVID A. · 2018 to 2022
$2.7M
Metastatic Clonal Heterogeneity and its Impact on Melanoma Therapeutic ResistanceR01CA236910 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HUGO, WILLY · 2020 to 2024
$2.3M
Identification and cloning of neoantigen-specific T cells for GBM immunotherapyR01CA222695 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PRINS, ROBERT M, XING, YI · 2019 to 2023
$2.0M
NCATS NIH HHS UL1 TR001881NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA211015NCI NIH HHS R01 CA222695NCI NIH HHS R01 CA227089NCI NIH HHS R01 CA236910NCI NIH HHS T32 CA009120
6 · The paper itself

Abstract

Primary brain tumors, such as glioblastoma (GBM), are remarkably resistant to immunotherapy, even though pre-clinical models suggest effectiveness. To understand this better in patients, here we take advantage of our recent neoadjuvant treatment paradigm to map the infiltrating immune cell landscape of GBM and how this is altered following PD-1 checkpoint blockade using high dimensional proteomics, single cell transcriptomics, and quantitative multiplex immunofluorescence. Neoadjuvant PD-1 blockade increases T cell infiltration and the proportion of a progenitor exhausted population of T cells found within the tumor. We identify an early activated and clonally expanded CD8+ T cell cluster whose TCR overlaps with a CD8+ PBMC population. Distinct changes are also observed in conventional type 1 dendritic cells that may facilitate T cell recruitment. Macrophages and monocytes still constitute the majority of infiltrating immune cells, even after anti-PD-1 therapy. Interferon-mediated changes in the myeloid population are consistently observed following PD-1 blockade; these also mediate an increase in chemotactic factors that recruit T cells. However, sustained high expression of T-cell-suppressive checkpoints in these myeloid cells continue to prevent the optimal activation of the tumor infiltrating T cells. Therefore, future immunotherapeutic strategies may need to incorporate the targeting of these cells for clinical benefit.

Indexed as

BrainBrain NeoplasmsDendritic CellsGlioblastomaHumansImmune Checkpoint InhibitorsNeoadjuvant TherapyNeoplasm Recurrence, LocalNeurosurgical ProceduresProgrammed Cell Death 1 ReceptorRNA-SeqSingle-Cell AnalysisT-LymphocytesTumor-Associated MacrophagesTumor EscapeImmune Checkpoint InhibitorsPDCD1 protein, humanProgrammed Cell Death 1 Receptor

Identifiers

PMID34836966
PMCPMC8626557
OpenAlexW3194247868

What OpenQuestion holds

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LicenceCC BY
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.