Evidence map›Paper›PMID 42040926›Full record

ArticleResearch square2026

Anti-VEGF vascular remodeling drives germinal center B cell-rich tertiary lymphoid structures during antibody-toxin and anti-CD40 combination therapy in glioblastoma.

Anjali Barnwal, Weixuan Yan, Sarah L Cook, Thomas Urup, Kevin Stevenson, Yiping He, Cristina Osorio, Scott Parker, Edwige Edouard, Michelle Bowie and 6 more

Abstract readPreprint
In one paragraph

Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Anjali BarnwalThe Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.ORCID 0000-0001-7190-8444
Weixuan YanThe Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.
Sarah L CookThe Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.ORCID 0000-0002-0516-9388
Thomas UrupDanish Comprehensive Cancer Center, Brain Tumor Center (DCCC-BTC), Blegdamsvej 9, Copenhagen, 2100, Denmark.
Kevin StevensonThe Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.
Yiping HeThe Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.
Cristina OsorioThe Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.
Scott ParkerThe Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.
Edwige EdouardThe Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.
Michelle BowieThe Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.
Hunter C JacksonThe Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.
Roger E McLendonThe Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.ORCID 0000-0001-6682-4588
Annick DesjardinsThe Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.ORCID 0000-0003-3869-8283
David M AshleyThe Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.ORCID 0000-0002-4754-5900
Darell D BignerThe Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.
Vidyalakshmi ChandramohanThe Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.ORCID 0000-0002-0653-3014

Funding

Synergistic microglial activation and tumor cell killing for improved GBM responseR01NS119183 · NINDS · DUKE UNIVERSITY · PI CHANDRAMOHAN, VIDYALAKSHMI · 2021 to 2025
$2.0M
Inflammasomes - a driver of sexual dimorphism to glioma therapiesR01NS141861 · NINDS · DUKE UNIVERSITY · PI Vidyalakshmi Chandramohan · 2025 to 2026
$822k
NINDS NIH HHS R01 NS119183NINDS NIH HHS R01 NS141861
6 · The paper itself

Abstract

Glioblastoma (GBM) is characterized by aberrant neovascularization and angiogenesis. Bevacizumab (Avastin), a monoclonal antibody targeting vascular endothelial growth factor (VEGF), is clinically used with chemotherapy for patients with GBM, yet its impact on the tumor immune microenvironment remains poorly understood. Transcriptomic profiling of matched pre- and post-treatment tumors from patients with recurrent GBM treated with bevacizumab plus the topoisomerase inhibitor irinotecan revealed significant immune reprogramming in responders, with post-treatment tumors displaying features indicative of tertiary lymphoid structure (TLS) formation and enhanced antitumor immunity. In preclinical orthotopic glioma models, combining αVEGF therapy with intratumoral epidermal growth factor receptor (EGFR)-targeted cytotoxic therapy and αCD40 immunotherapy normalized the tumor vasculature, promoted lymphatic vessel growth, induced tumor cell killing, increased intratumoral T cells, plasma cells, germinal center B cells, and antigen-presenting and tissue-repair-associated macrophages, while reducing immunosuppression and supporting mature TLS formation with an antitumor immune phenotype. Functionally, the tumor-, immune-, and vascular-targeted combination therapy significantly improved tumor control, extended survival, and induced durable antitumor memory in glioma models. Collectively, these results identify VEGF as a central regulator of the vascular-immune axis during cytotoxic EGFR+αCD40 therapy in GBM and provide a strong rationale for combining vascular-, tumor-, and immune-targeted approaches to overcome therapeutic resistance and improve outcomes for patients with GBM.

Identifiers

PMID42040926
PMCPMC13105118

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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.