Evidence map›Paper›PMID 42675603›Full record

ArticleNeuro-oncology2026

A CAR-T Tonic Signaling Code Predicts Anti-Tumor Efficacy in Diffuse Midline Glioma.

Bing Deng, Xiaowen Zhong, Dazhuan Xin, Xiao Huang, Upendra K Soni, Wenkun Ma, Mingjun Cai, Po-Yu Liang, Jun Bai, Qian Qin and 16 more

Abstract read
PubMed Publisher
In one paragraph

Article in Neuro-oncology, 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

5 · Who and what money

Authors and funding

26 authors.

Bing DengDepartment of Pediatrics, O'Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL 35205, USA.
Xiaowen ZhongDepartment of Pediatrics, O'Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL 35205, USA.
Dazhuan XinDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Xiao HuangDepartment of Pediatrics, O'Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL 35205, USA.
Upendra K SoniDepartment of Pediatrics, O'Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL 35205, USA.
Wenkun MaDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA.
Mingjun CaiDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA.
Po-Yu LiangDepartment of Computer Science, University of Cincinnati, Cincinnati, Ohio, USA.
Jun BaiDepartment of Computer Science, University of Cincinnati, Cincinnati, Ohio, USA.
Qian QinBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Shreya MishraDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Ming HuDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Arman E BayatDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA.
Zaili LuoDepartment of Pediatrics, O'Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL 35205, USA.
Jiajie DiaoDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Mei XinDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA.
Natasha Pillay-SmileyThe Cure Starts Now Brain Tumor Center, Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Trent R HummelThe Cure Starts Now Brain Tumor Center, Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Charles B StevensonDivision of Pediatric Neurosurgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Jessica B FosterDivision of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.
Peter de BlankThe Cure Starts Now Brain Tumor Center, Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Scott RaskinThe Cure Starts Now Brain Tumor Center, Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Carl KoschmannDepartment of Pediatrics, Michigan Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Jose A CancelasReilly and O'Connell Families Cell Manipulation Core Facility and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Yi ZhengDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA.
Q Richard LuDepartment of Pediatrics, O'Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL 35205, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDiffuse middle glioma (DMG or DIPG) is a fatal pediatric brain tumor. Although chimeric antigen receptor (CAR) T-cell therapy shows promise, clinical outcomes remain inconsistent due to premature exhaustion, underscoring a critical need to improve CAR-T persistence. A major barrier to CAR-T efficacy is antigen-independent tonic signaling, yet the extent to which tonic signaling shapes CAR-T durability and clinical outcomes, particularly in DMG, remains incompletely defined.

methodsUsing a clinically investigated B7-H3 MGA271-based CAR as a reference platform, we generated alternative B7-H3 CARs incorporating either a human codon-optimized 376.96 (B7H3.BC) or Hu8H9 scFv antigen binding domain to systematically assess scFv-dependent effects on tonic signaling and therapeutic efficacy. CAR-T cells were evaluated using integrated in vitro and in vivo functional assays, alongside multi-omics profiling and computational modeling. We further derived a tonic signaling-associated gene signature and evaluated its predictive performance across independent clinical datasets.

resultsB7H3.BC CAR-T cells exhibit markedly restrained tonic signaling compared with MGA271- and Hu8H9-based counterparts, accompanied by superior antitumor activity and enhanced persistence across patient-derived DMG cells. Integrated multi-omics and single-cell profiling further identified a tonic signaling-associated gene signature that outperforms conventional T-cell exhaustion signatures in predicting therapeutic efficacy across multiple clinical trials, including DMG and other tumors.

conclusionsOur findings establish that scFv-dependent modulation of tonic signaling critically governs CAR-T persistence and antitumor efficacy in DMG. By linking CAR design to transcriptional and epigenetic programs, our study provides a principle-based and predictive framework to inform rational CAR engineering and improve therapeutic outcomes.

Indexed as

CAR-T cell therapyDMG/DIPGimmunotherapypredictive biomarkertonic signaling

Identifiers

PMID42675603

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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.