Evidence map›Paper›PMID 40404658›Full record

ArticleNature communications2025

Glioma-neuronal circuit remodeling induces regional immunosuppression.

Takahide Nejo, Saritha Krishna, Akane Yamamichi, Senthilnath Lakshmanachetty, Christian Jimenez, Kevin Y Lee, Donovan L Baker, Jacob S Young, Tiffany Chen, Su Su Sabai Phyu and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

42 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  3. Abundant CD8British journal of cancer · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Takahide NejoDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9191-8823
Saritha KrishnaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Akane YamamichiDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Senthilnath LakshmanachettyDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Christian JimenezDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Kevin Y LeeDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Donovan L BakerDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0009-0008-6928-3252
Jacob S YoungDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Tiffany ChenDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Su Su Sabai PhyuDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Lan PhungDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Marco GallusDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Gabriella C MaldonadoDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0009-0007-2277-3070
Kaori OkadaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Hirokazu OginoDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-2446-8789
Payal B WatchmakerDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
David DieboldDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Abrar ChoudhuryDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-8312-2457
Andy G S DanielDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Cathryn R CadwellDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1963-8285
David R RaleighDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-9299-8864
Shawn L Hervey-JumperDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA. shawn.hervey-jumper@ucsf.edu.ORCID http://orcid.org/0000-0003-4699-260X
Hideho OkadaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA. hideho.okada@ucsf.edu.ORCID http://orcid.org/0000-0003-0076-9920

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Alan Ashworth · 1999 to 2026
$209.7M
Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2002 to 2026
$57.4M
Training Program in Translational Brain Tumor ResearchT32CA151022 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2010 to 2026
$6.6M
Preclinical development of breakthrough immunotherapy for brain tumorsR35NS105068 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI OKADA, HIDEHO · 2018 to 2025
$6.0M
Cortical information loss in diffuse low-grade glioma infiltrated cortexR01NS137950 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Shawn L. Hervey-Jumper · 2024 to 2026
$1.2M
The role of retinoic acid signaling in patterning the human cerebral cortexK08NS126573 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Cathryn Rene Cadwell · 2022 to 2026
$1.2M
Intratumoral functional connectivity with implications on synaptogenesis and aphasia recovery in adult astrocytic WHO II-III gliomaK08NS110919 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HERVEY-JUMPER, SHAWN L. · 2019 to 2023
$1.0M
Illumina NovaSeq 6000 Sequencing SystemS10OD028511 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOW, ERIC D · 2020 to 2020
$583k
NCI NIH HHS P30 CA082103NCI NIH HHS P50 CA097257NCI NIH HHS T32 CA151022NIH HHS S10 OD028511NINDS NIH HHS K08 NS110919NINDS NIH HHS K08 NS126573NINDS NIH HHS R01 NS137950NINDS NIH HHS R35 NS105068
6 · The paper itself

Abstract

Neuronal activity-driven mechanisms influence glioblastoma cell proliferation and invasion, while glioblastoma remodels neuronal circuits. Although a subpopulation of malignant cells enhances neuronal connectivity, their impact on the immune system remains unclear. Here, we show that glioblastoma regions with enhanced neuronal connectivity exhibit regional immunosuppression, characterized by distinct immune cell compositions and the enrichment of anti-inflammatory tumor-associated macrophages (TAMs). In preclinical models, knockout of Thrombospondin-1 (TSP1/Thbs1) in glioblastoma cells suppresses synaptogenesis and glutamatergic neuronal hyperexcitability. Furthermore, TSP1 knockout restores antigen presentation-related genes, promotes the infiltration of pro-inflammatory TAMs and CD8 + T-cells in the tumor, and alleviates TAM-mediated T-cell suppression. Pharmacological inhibition of glutamatergic signaling also shifts TAMs toward a less immunosuppressive state, prolongs survival in mice, and shows the potential to enhance the efficacy of immune cell-based therapy. These findings confirm that glioma-neuronal circuit remodeling is strongly linked with regional immunosuppression and suggest that targeting glioma-neuron-immune crosstalk could provide avenues for immunotherapy.

Indexed as

Brain NeoplasmsGlioblastomaGliomaImmune ToleranceNeuronsAnimalsCD8-Positive T-LymphocytesCell Line, TumorFemaleHumansImmunosuppression TherapyMaleMiceMice, Inbred C57BLMice, KnockoutThrombospondin 1Thrombospondin 1

Identifiers

PMID40404658
PMCPMC12098748

What OpenQuestion holds

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Registered trials

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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.