Evidence map›Paper›PMID 29262845›Full record

ArticleGenome biology2017

Single-cell profiling of human gliomas reveals macrophage ontogeny as a basis for regional differences in macrophage activation in the tumor microenvironment.

Sören Müller, Gary Kohanbash, S John Liu, Beatriz Alvarado, Diego Carrera, Aparna Bhaduri, Payal B Watchmaker, Garima Yagnik, Elizabeth Di Lullo, Martina Malatesta and 6 more

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 437 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
437citing papers in PubMed, 1 pooled it
16.3field-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

437 citing papers in PubMed, 1 synthesis or guideline pooled it, 668 citations in OpenAlex.

  1. Pooled it
  2. Oncoimmunology · 2026
    Article
  3. Review
  4. Review
  5. FAPExperimental & molecular medicine · 2026
    Article
  6. Article
  7. Immunotherapy for Glioma: A compartmental framework for resistance and rational combination design.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
  8. Review
  9. Macrophage Plasticity in Cancer Therapy: Function, Timing, and Tradeoffs.International journal of molecular sciences · 2026
    Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Single-cell and bulk transcriptome analysis reveals the impact of inflammatory microglia on prognosis and immunotherapy response in primary glioblastoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  15. Article
  16. Exosomal NEAT1 from tumor stem cells induces SIRPAJournal of experimental & clinical cancer research : CR · 2026
    Article
  17. Review
  18. Review
  19. Article
  20. Accumulation of Siglec10European journal of immunology · 2026
    Article

377 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

16 authors at 3 institutions in 1 country.

Sören MüllerDepartment of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.
Gary KohanbashDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, 15261, USA. Gary.Kohanbash@pitt.edu.
S John LiuDepartment of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.
Beatriz AlvaradoDepartment of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.
Diego CarreraDepartment of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.
Aparna BhaduriEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, 94158, USA.
Payal B WatchmakerDepartment of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.
Garima YagnikDepartment of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.
Elizabeth Di LulloEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, 94158, USA.
Martina MalatestaDepartment of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.
Nduka M AmankulorDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Arnold R KriegsteinEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, 94158, USA.
Daniel A LimDepartment of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.
Manish AghiDepartment of Neurological Surgery, University of California, San Francisco, CA, 94143, USA. manish.aghi@ucsf.edu.
Hideho OkadaDepartment of Neurological Surgery, University of California, San Francisco, CA, 94143, USA. hideho.okada@ucsf.edu.
Aaron DiazDepartment of Neurological Surgery, University of California, San Francisco, CA, 94143, USA. aaron.diaz@ucsf.edu.ORCID http://orcid.org/0000-0001-9059-9501
University of California, San Francisco · USUniversity of Pittsburgh · USSan Francisco VA Medical Center · US

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer Leigh Clarke · 1999 to 2026
$209.7M
Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2002 to 2026
$57.4M
Development and Expansion of the Human Cerebral CortexR35NS097305 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRIEGSTEIN, ARNOLD · 2017 to 2024
$8.5M
NCI NIH HHS P30 CA082103NCI NIH HHS P50 CA097257NIH HHS P30-CA82103-18NIH HHS P50-CA097257-13:7017
6 · The paper itself

Abstract

backgroundTumor-associated macrophages (TAMs) are abundant in gliomas and immunosuppressive TAMs are a barrier to emerging immunotherapies. It is unknown to what extent macrophages derived from peripheral blood adopt the phenotype of brain-resident microglia in pre-treatment gliomas. The relative proportions of blood-derived macrophages and microglia have been poorly quantified in clinical samples due to a paucity of markers that distinguish these cell types in malignant tissue.

resultsWe perform single-cell RNA-sequencing of human gliomas and identify phenotypic differences in TAMs of distinct lineages. We isolate TAMs from patient biopsies and compare them with macrophages from non-malignant human tissue, glioma atlases, and murine glioma models. We present a novel signature that distinguishes TAMs by ontogeny in human gliomas. Blood-derived TAMs upregulate immunosuppressive cytokines and show an altered metabolism compared to microglial TAMs. They are also enriched in perivascular and necrotic regions. The gene signature of blood-derived TAMs, but not microglial TAMs, correlates with significantly inferior survival in low-grade glioma. Surprisingly, TAMs frequently co-express canonical pro-inflammatory (M1) and alternatively activated (M2) genes in individual cells.

conclusionsWe conclude that blood-derived TAMs significantly infiltrate pre-treatment gliomas, to a degree that varies by glioma subtype and tumor compartment. Blood-derived TAMs do not universally conform to the phenotype of microglia, but preferentially express immunosuppressive cytokines and show an altered metabolism. Our results argue against status quo therapeutic strategies that target TAMs indiscriminately and in favor of strategies that specifically target immunosuppressive blood-derived TAMs.

Indexed as

AnimalsComputational BiologyGene Expression ProfilingGene Expression Regulation, NeoplasticGene OntologyGliomaHigh-Throughput Nucleotide SequencingHumansImmunotherapyMacrophage ActivationMacrophagesMicePrognosisSingle-Cell AnalysisSurvival AnalysisTranscriptomeGliomaImmunotherapyMacrophageSingle-cell sequencing

Identifiers

PMID29262845
PMCPMC5738907
OpenAlexW2778033786

What OpenQuestion holds

Textmetadata
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.