Evidence map›Paper›PMID 42666105›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Crosstalk Between CTSB

Hao Zhang, Nan Zhang, Xisong Liang, Jie Wen, Ziyu Dai, Wantao Wu, Shuyu Li, Songshan Feng, Zaoqu Liu, Zhiwei Xia and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 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

12 authors.

Hao Zhang *Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.ORCID https://orcid.org/0000-0002-4582-2556
Nan Zhang *Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.ORCID https://orcid.org/0000-0001-6518-2501
Xisong LiangDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.ORCID https://orcid.org/0000-0001-6056-1609
Jie WenDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.ORCID https://orcid.org/0000-0002-2323-5932
Ziyu DaiDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.ORCID https://orcid.org/0000-0003-2855-741X
Wantao WuDepartment of Thyroid and Breast Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.ORCID https://orcid.org/0009-0008-9501-2819
Shuyu LiDepartment of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.ORCID https://orcid.org/0009-0007-2527-4234
Songshan FengDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.ORCID https://orcid.org/0000-0001-6593-9260
Zaoqu LiuInstitute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.ORCID https://orcid.org/0000-0002-0452-742X
Zhiwei XiaDepartment of Neurology, Hunan Aerospace Hospital, Hunan Normal University, Changsha, China.ORCID https://orcid.org/0000-0001-8880-4617
Peng LuoDepartment of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.ORCID https://orcid.org/0000-0002-8215-2045
Quan ChengDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.ORCID https://orcid.org/0000-0003-2401-5349

Funding

Beijing Xisike Clinical Oncology Research Foundation Gilead2024-PT-0070Chongqing Medical Youth Top Talent Program YXQN202558Chongqing Youth Innovation Talent Project CSTB2025YITP-QCRCX0096Jiangxi Provincial Health Technology Project 202510008Jiangxi Provincial Natural Science Foundation 20252BAC220048Key R&D Program of Jiangxi Province 20243BBI91007National Natural Science Foundation of China 82303610National Natural Science Foundation of China 82372943National Natural Science Foundation of China 82503442Science and Technology Innovation Program of Hunan Province 2023RC3074
6 · The paper itself

Abstract

backgroundGlioblastoma (GBM) establishes a highly immunosuppressive microenvironment through intricate molecular dialogues with tumor-associated macrophages (TAMs), contributing to immunotherapy resistance.

methodsWe integrated advanced biological network analyses with multimodal AI to identify CTSB as a key biomarker. Functional validation included GBM-macrophage co-culture systems, chromatin immunoprecipitation (ChIP), dual-luciferase reporter assays, molecular docking, and co-immunoprecipitation (Co-IP). In vivo experiments employed orthotopic (GL261 and CT-2A) and subcutaneous GBM models with lentivirus-mediated CTSB knockdown and anti-PD-1 therapy. Tumor microenvironment dynamics were assessed via in-house generated single-cell RNA sequencing and multiplex immunofluorescence.

resultsCathepsin B (CTSB) was identified as a critical driver of aggressive GBM progression and poor outcomes. Mechanistically, macrophage-derived IL-6 activates STAT3 in tumor cells, upregulating CTSB expression. Structural and Co-IP analyses revealed CTSB, secreted by tumor cells, binds the C-terminus of macrophage S100A10, reinforcing IL-6 secretion, forming a feedforward loop between CTSB

conclusionsThis study unveils a targetable GBM-macrophage signaling axis, proposing CTSB inhibition as a strategy to enhance immunotherapy efficacy in GBM patients.

Indexed as

Annexin A2Brain NeoplasmsGlioblastomaImmunotherapyMacrophagesS100 ProteinsTumor-Associated MacrophagesAnimalsCell Line, TumorHumansImmune EvasionMiceS100 Calcium Binding Protein A10Tumor MicroenvironmentAnnexin A2S100 Calcium Binding Protein A10S100 ProteinsCTSBglioblastomaimmunotherapyS100A10tumor‐associated macrophage

Identifiers

PMID42666105
PMCPMC13525416

What OpenQuestion holds

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Read underepoch 390

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 OpenQuestion graph.