Evidence map›Paper›PMID 40677211›Full record

ArticleCNS neuroscience & therapeutics2025

Inhibition of NFE2L1 Enables the Tumor-Associated Macrophage Polarization and Enhances Anti-PD1 Immunotherapy in Glioma.

Qun Zhang, Qiusi Tian, Rongzhen Deng, Keli Liu, Shiqun Chen, Shaofan Hu, Zhengwen Zhang, Hongzhao Lu, Yiguo Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
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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.

Qun ZhangThe Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Medical Sciences, Chongqing University, Chongqing, China.
Qiusi TianDepartment of Neurosurgery, 3201 Hospital of Xi'an Jiaotong University Health Science Center, Hanzhong, China.
Rongzhen DengThe Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Medical Sciences, Chongqing University, Chongqing, China.
Keli LiuThe Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Medical Sciences, Chongqing University, Chongqing, China.
Shiqun ChenThe Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Medical Sciences, Chongqing University, Chongqing, China.
Shaofan HuThe Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Medical Sciences, Chongqing University, Chongqing, China.
Zhengwen ZhangLaboratory of Neuroscience, Institute of Cognitive Neuroscience and School of Pharmacy, University College London, London, UK.
Hongzhao LuSchool of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong, China.
Yiguo ZhangThe Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Medical Sciences, Chongqing University, Chongqing, China.ORCID 0000-0003-3910-2779

Funding

National Natural Science Foundation of China 81872336National Natural Science Foundation of China 82073079Natural Science Foundation of Shaanxi Province 2023-JC-QN-0992
6 · The paper itself

Abstract

BACKGROUND AND

objectivesA pivotal role of cancer (e.g., glioma) microenvironment is primarily executed by tumor-associated macrophages (TAMs) in facilitating cancer immune evasion and even resisting immunotherapies. However, the molecular base for governing such functionality of TAMs remains poorly understood. Thereby, we here explore the impact of such a key regulatory transcription factor NFE2L1 (also called Nrf1) on glioma-relevant TAMs.

methodsA set of combining in vivo and in vitro experimental approaches, e.g., by utilizing CRISPR-Cas9 and overexpression plasmids to modulate NFE2L1 expression, and the resulting phenotypic changes in TAMs were evaluated. Besides, immunofluorescence, RT-qPCR and flow cytometry were conducted to assay the infiltration of various immune cells, such as CD8+ T cells and M1-type macrophages, in the glioma microenvironment, as well as their therapeutic response to anti-PD1 treatment.

resultsDeficiency of NFE2L1 causes a unique phenotypic switch in the TAMs from its pro-cancer M2-type to another anti-cancer M1-type, thereby inhibiting malignant progression of glioma. Such NFE2L1-deficiency leads to significantly increases of CD8+ T cells and M1 macrophages within tumor tissues of glioma and hence enhances its sensitivity to anti-PD1 therapy. Further experimental evidence has provided revealing a synergistic efficacy triggered by combined therapy of CD38 inhibitor with PD1 antibodies, significantly inhibited tumor growth, compared to that of their monotherapy. The mechanistic study unraveled that NFE2L1 enables for directly binding to those ARE sites within the promoter regions of both CD38 and PD-L1 genes in order to govern their transcriptional expression.

conclusionsThe aberrant role of NFE2L1 in the malignant progression of glioma was discovered in this study. It is of crucial significance to emphasize the potential of NFE2L1 inhibition as a strategic approach to enhance the efficacy of immunotherapeutic intervention. Overall, this discovery holds a substantial promise for advancement of innovative combination therapies, potentially enhancing treatment outcomes for individuals afflicted with glioma.

Indexed as

Brain NeoplasmsGliomaImmune Checkpoint InhibitorsImmunotherapyProgrammed Cell Death 1 ReceptorTumor-Associated MacrophagesAnimalsCell Line, TumorHumansMiceMice, Inbred C57BLTumor MicroenvironmentImmune Checkpoint InhibitorsProgrammed Cell Death 1 Receptoranti‐PD1gliomaNFE2L1tumor‐associated macrophages

Identifiers

PMID40677211
PMCPMC12271640

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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.