Evidence map›Paper›PMID 38844770›Full record

ArticleNature communications2024

Ultrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas.

Víctor A Arrieta, Andrew Gould, Kwang-Soo Kim, Karl J Habashy, Crismita Dmello, Gustavo I Vázquez-Cervantes, Irina Palacín-Aliana, Graysen McManus, Christina Amidei, Cristal Gomez and 23 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 2 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

56 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  4. Pharmacokinetic Analysis of Carboplatin and Fluorescein Brain Retention following Ultrasound-Based Blood-Brain Barrier Opening.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
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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

33 authors.

Víctor A ArrietaDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Andrew GouldDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Kwang-Soo KimDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Karl J HabashyDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Crismita DmelloDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-1688-9663
Gustavo I Vázquez-CervantesDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Irina Palacín-AlianaDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Graysen McManusDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0009-0001-0298-0191
Christina AmideiDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Cristal GomezDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Silpol DhiantravanDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Li ChenDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Daniel Y ZhangDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Ruth SagantyDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Meghan E CholakDepartment of Medicine, Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Surya PandeyDepartment of Medicine, Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Matthew McCordDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Kathleen McCortneyDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0000-0001-7085-830X
Brandyn CastroDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Rachel WardDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Miguel MuzzioLife Sciences Group, IIT Research Institute, Chicago, IL, USA.
Guillaume BouchouxCarthera, Lyon, France.
Carole DesseauxCarthera, Lyon, France.
Michael CanneyCarthera, Lyon, France.
Alexandre CarpentierSorbonne Université, Inserm, CNRS, UMR S 1127, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, Service de Neurochirurgie, Paris, France.
Bin ZhangDepartment of Medicine, Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-6631-7647
Jason M MiskaDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0000-0001-9608-2810
Maciej S LesniakDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-0096-5107
Craig M HorbinskiDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0000-0001-8340-9992
Rimas V LukasNorthwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Roger StuppDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-5483-3118
Catalina Lee-ChangDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. catalina.leechang@northwestern.edu.ORCID http://orcid.org/0000-0002-7675-2124
Adam M SonabendDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. adam.sonabend@northwestern.edu.ORCID http://orcid.org/0000-0002-8347-1945

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Devalingam Mahalingam · 1993 to 2026
$153.9M
STINGing GBM: A First-in- Man Clinical Trial in Surgical Resectable Recurrent GBMP50CA221747 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Hui Zhang · 2018 to 2026
$21.4M
Leveraging doxorubicin immune-modulation, blood-brain barrier opening, and personalized medicine for effective immunotherapy in glioblastoma. A mechanistic approach and pharmacokinetic trial.U19CA264338 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Adam M Sonabend · 2021 to 2026
$5.8M
Blood-brain barrier disruption with implantable ultrasound to enhance paclitaxel delivery: A Phase 1-2 clinical trial in recurrent glioblastomaR01CA245969 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Adam M Sonabend, Roger Stupp · 2020 to 2026
$2.8M
Development of B-cell-based vaccine for GlioblastomaR37CA258426 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Catalina Lee Chang · 2021 to 2026
$2.2M
MAPK as target of glioma immunoediting by CD8 T-cells, and predictor of response to immunotherapyR01NS110703 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SONABEND, ADAM M · 2020 to 2024
$1.9M
Mechanisms and therapeutic implications of temozolomide resistance in glioblastomaF32CA264883 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MCCORD, MATTHEW · 2022 to 2023
$148k
NCI NIH HHS F32 CA264883NCI NIH HHS P30 CA060553NCI NIH HHS P50 CA221747NCI NIH HHS R01 CA245969NCI NIH HHS R37 CA258426NCI NIH HHS U19 CA264338NINDS NIH HHS R01 NS110703U.S. Department of Health & Human Services | National Institutes of Health (NIH) 1R01NS110703-01A1U.S. Department of Health & Human Services | National Institutes of Health (NIH) 1U19CA264338-01U.S. Department of Health & Human Services | National Institutes of Health (NIH) P50CA221747U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1R01CA245969-01A1
6 · The paper itself

Abstract

Given the marginal penetration of most drugs across the blood-brain barrier, the efficacy of various agents remains limited for glioblastoma (GBM). Here we employ low-intensity pulsed ultrasound (LIPU) and intravenously administered microbubbles (MB) to open the blood-brain barrier and increase the concentration of liposomal doxorubicin and PD-1 blocking antibodies (aPD-1). We report results on a cohort of 4 GBM patients and preclinical models treated with this approach. LIPU/MB increases the concentration of doxorubicin by 2-fold and 3.9-fold in the human and murine brains two days after sonication, respectively. Similarly, LIPU/MB-mediated blood-brain barrier disruption leads to a 6-fold and a 2-fold increase in aPD-1 concentrations in murine brains and peritumoral brain regions from GBM patients treated with pembrolizumab, respectively. Doxorubicin and aPD-1 delivered with LIPU/MB upregulate major histocompatibility complex (MHC) class I and II in tumor cells. Increased brain concentrations of doxorubicin achieved by LIPU/MB elicit IFN-γ and MHC class I expression in microglia and macrophages. Doxorubicin and aPD-1 delivered with LIPU/MB results in the long-term survival of most glioma-bearing mice, which rely on myeloid cells and lymphocytes for their efficacy. Overall, this translational study supports the utility of LIPU/MB to potentiate the antitumoral activities of doxorubicin and aPD-1 for GBM.

Indexed as

Blood-Brain BarrierBrain NeoplasmsDoxorubicinMicrobubblesProgrammed Cell Death 1 ReceptorAnimalsAntibodies, Monoclonal, HumanizedBrainCell Line, TumorDrug Delivery SystemsFemaleGlioblastomaGliomaHumansImmune Checkpoint InhibitorsMaleAntibodies, Monoclonal, HumanizedDoxorubicinImmune Checkpoint Inhibitorsliposomal doxorubicinPDCD1 protein, humanpembrolizumabPolyethylene GlycolsProgrammed Cell Death 1 Receptor

Identifiers

PMID38844770
PMCPMC11156895

What OpenQuestion holds

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Read underepoch 390

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.