Evidence map›Paper›PMID 40373963›Full record

ArticleJournal of advanced research2026

Targeting mesenchymal monocyte-derived macrophages to enhance the sensitivity of glioblastoma to temozolomide by inhibiting TNF/CELSR2/p65/Kla-HDAC1/EPAS1 axis.

Wei Gao, Xinmiao Long, Xiang Lin, Kun Deng, Danyang Li, Meng Huang, Xiangyu Wang, Qing Liu, Minghua Wu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
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

9 authors.

Wei GaoThe Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, China; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, China.
Xinmiao LongThe Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, China; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, China.
Xiang LinThe Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, China; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, China.
Kun DengThe Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, China; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, China.
Danyang LiThe Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, China; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, China.
Meng HuangDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
Xiangyu WangDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
Qing LiuDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China. Electronic address: liuqingdr@csu.edu.cn.
Minghua WuThe Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, China; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, China; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China; Xiangya School of Public Health, Central South University, Changsha, China. Electronic address: wuminghua554@aliyun.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionTemozolomide (TMZ) resistance poses a significant challenge to the treatment of aggressive and highly lethal glioblastomas (GBM). Monocyte-derived Macrophages (MDM) within the tumor microenvironment are key factors contributing to TMZ resistance in GBM. Lactate-mediated histone lysine lactylation (Kla) plays a crucial role in the regulation of tumor progression. However, the mechanism through which MDM-induced Kla expression promotes TMZ resistance in GBM remains unclear.

objectivesThe objective of this study s to identify a subtype of MDM with therapeutic potential target and to elucidate the mechanisms through which this subtype of MDM contributes to tumor malignant progression and TMZ resistance.

methodsWe integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics data to evaluate whether mesenchymal (MES) MDM is associated with poor prognosis. By establishing a subtype model of GBM cells for the first time, we validated the mechanism by which MES-MDM promotes subtype conversion of tumor cells. Using patient-derived GBM organoids and an intracranial orthotopic GBM model, we demonstrated that targeting MES-MDM increased GBM sensitivity to TMZ treatment.

resultsWe identified a novel MDM subtype, MES-MDM, in the hypoxic niches of the perinecrotic region characterized by high TREM1 expression, which fueled GBM progression. Hypoxia drived MES-MDM signatures by activating ATF3 transcription. MES-MDM facilitated the transition from the NPC to the MES subtype in GBM cells, in which Histone Deacetylase 1 (HDAC1) Kla, induced by the TNF-CELSR2/p65 signaling pathway, promoted this conversion, thereby promoting TMZ resistance. Targeting MES-MDM with TREM1 inhibitory peptides amplified TMZ sensitivity, offering a potential strategy for overcoming resistance to therapy in GBM. Targeting TREM1 enhanced the effectiveness of anti-PD-1 immunotherapy.

conclusionThis study provides a potential therapeutic strategy for patients with MES-subtype GBM by targeting MES-MDM in combination with TMZ or PD-1 antibody treatment.

Indexed as

Brain NeoplasmsDrug Resistance, NeoplasmGlioblastomaMacrophagesTemozolomideAnimalsAntineoplastic Agents, AlkylatingCell Line, TumorGene Expression Regulation, NeoplasticHistone Deacetylase 1HumansMiceSignal TransductionTumor MicroenvironmentTumor Necrosis Factor-alphaAntineoplastic Agents, AlkylatingHDAC1 protein, humanHistone Deacetylase 1TemozolomideTumor Necrosis Factor-alphaGlioblastomaHypoxiaLactylationMonocyte-derived macrophagesTemozolomide resistance

Identifiers

PMID40373963
PMCPMC12869204

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.