Evidence map›Paper›PMID 41256549›Full record

ArticlebioRxiv : the preprint server for biology2025

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

Emily B Deng, Xiaowen Zhong, Dazhuan Xin, Upendra K Soni, Wenkun Ma, Xiao Huang, Mingjun Cai, Po-Yu Liang, Jun Bai, Qian Qin and 15 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Emily B DengDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Xiaowen ZhongDepartment of Pediatrics, The Cure Starts Now Brain Tumor Center, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Dazhuan XinDepartment of Pediatrics, The Cure Starts Now Brain Tumor Center, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Upendra K SoniDepartment of Pediatrics, The Cure Starts Now Brain Tumor Center, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Wenkun MaDepartment of Pediatrics, The Cure Starts Now Brain Tumor Center, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Xiao HuangDepartment of Pediatrics, The Cure Starts Now Brain Tumor Center, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Mingjun CaiDepartment of Pediatrics, The Cure Starts Now Brain Tumor Center, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, 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.ORCID 0000-0002-2119-6263
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, The Cure Starts Now Brain Tumor Center, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Jiajie DiaoDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Mei XinDepartment of Pediatrics, The Cure Starts Now Brain Tumor Center, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Natasha Pillay-SmileyDepartment of Pediatrics, The Cure Starts Now Brain Tumor Center, Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Trent R HummelDepartment of Pediatrics, The 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 BlankDepartment of Pediatrics, The Cure Starts Now Brain Tumor Center, Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.ORCID 0000-0001-6623-3040
Scott RaskinDepartment of Pediatrics, The Cure Starts Now Brain Tumor Center, Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Carl KoschmannDepartment of Pediatrics, Michigan Medicine, Ann Arbor, MI, USA; 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, The Cure Starts Now Brain Tumor Center, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Q Richard LuDepartment of Pediatrics, The Cure Starts Now Brain Tumor Center, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

Funding

Molecular Mechanisms of Oligodendrocyte Myelination and remyelinationR01NS142389 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI QING Richard LU, Mei Xin · 2025 to 2026
$1.2M
Glial Origin and Signaling in MedulloblastomaR01NS140460 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI QING Richard LU, Mei Xin · 2025 to 2026
$1.2M
NINDS NIH HHS R01 NS140460NINDS NIH HHS R01 NS142389
6 · The paper itself

Abstract

Diffuse midline glioma (DIPG/DMG) is a uniformly fatal pediatric brain tumor with no effective cure. Although CAR T-cell therapy shows promise, clinical outcomes remain inconsistent due to limited persistence and premature exhaustion. Reliable predictive biomarkers are lacking, and proposed exhaustion or stemness markers provide limited utility. Here, we systematically compare multiple CAR-T constructs targeting clinically-relevant antigen B7-H3 and identify antigen-independent CAR activation, or tonic signaling, as a key determinant of therapeutic performance. We find that B7-H3 CAR-T cells with restrained tonic signaling display superior tumor killing, persistence, and resistance to exhaustion, along with reduced CAR membrane clustering, in patient-derived DIPG models. Integrated multi-omics and single-cell profiling further reveal a CAR-T tonic signaling-associated gene signature that outperforms conventional exhaustion or stemness markers in predicting therapeutic efficacy across multiple clinical trials, including DIPG and other tumor types. Together, these findings define a mechanistic and predictive framework to guide CAR design and improve clinical outcomes.

Identifiers

PMID41256549
PMCPMC12621713

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.