ArticleJournal of experimental & clinical cancer research : CR2022
Exosomal circZNF451 restrains anti-PD1 treatment in lung adenocarcinoma via polarizing macrophages by complexing with TRIM56 and FXR1.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 71 citations in OpenAlex.
- Exosomal circular RNAs in the tumor immune microenvironment: From regulatory mechanisms to therapeutic opportunities and translational hurdles (Review).International journal of molecular medicine · 2026Review
- A T-cell exhaustion-related signature for predicting response to immunotherapy among patients with lung adenocarcinoma.Translational lung cancer research · 2026Article
- Circular RNAs in NSCLC: Their Role in Tumorigenesis, Tumor Microenvironment Reshaping, and Response to Therapies.Cancers · 2026Review
- Novel Insights into the Role of circRNAs in Cancer Immunotherapy Resistance and Clinical Implications.International journal of molecular sciences · 2026Review
- Circular RNAs in cancer: Its biogenesis, functions, relationships with cancer progression, applications in immunotherapy and biomarker potentials.Cancer immunology, immunotherapy : CII · 2026Review
- Single-Cell Transcriptomics Identifies BST2 as an Oncogenic Driver and Immunotherapy Biomarker in Lung Adenocarcinoma.Mediators of inflammation · 2026Article
- The Transcriptional Role of Circular RNAs in Drug Resistance by Modulating the miRNA/mRNA Axis.Experientia supplementum (2012) · 2026Article
- Exosomal regulation of cellular reprogramming and polarization in the tumor microenvironment.Cancer cell international · 2025Review
- TRIM32 promotes tumor immune evasion and impedes Anti-PD-1 treatment by inducing immunosuppressive macrophages in gastric cancer.Journal of translational medicine · 2025Article
- Unraveling the molecular-pathological characteristics and cellular complexity of the tumor immune microenvironment in metastatic non-small cell lung cancer.Cell communication and signaling : CCS · 2025Review
- CircRNAs: functions and emerging roles in cancer and immunotherapy.BMC medicine · 2025Review
- Article
- Emerging roles of non-coding RNA derived from extracellular vesicles in regulating PD-1/PD-L1 pathway: insights into cancer immunotherapy and clinical applications.Cancer cell international · 2025Review
- *Mechanisms of circular RNA in drug resistance of lung cancer: therapeutic targets, biomarkers, and future research directions.Discover oncology · 2025Review
- Transcription factor ELF4 in physiology and diseases: Molecular roles and clinical implications.Genes & diseases · 2025Review
- Exosomal circRNAs: key modulators in breast cancer progression.Cell death discovery · 2025Review
- Comprehensive analysis of TRIM56's prognostic value and immune infiltration in Pan-Cancer.Scientific reports · 2025Article
- Cell components of tumor microenvironment in lung adenocarcinoma: Promising targets for small-molecule compounds.Chinese medical journal · 2025Review
- TRIM56 Promotes White Adipose Tissue Browning to Attenuate Obesity by Degrading TLE3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Extracellular vesicles in tumor immunity: mechanisms and novel insights.Molecular cancer · 2025Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundAlthough success was achieved in the therapy for a minority of advanced lung adenocarcinoma (LUAD) patients, anti-programmed death 1 (PD1) resistance was found in most LUAD patients. Here, we aimed to uncover a potential role of exosomal circular RNAs (circRNAs) in LUAD refractory to PD1 blockade.
methodscircRNA sequencing and qRT-PCR were performed to determine the level of exosomal circRNAs in LUAD patients subsequently treated with anti-PD1. Then, the RNA pulldown, RNA immunoprecipitation, mass spectrometry, chromatin immunoprecipitation, luciferase reporter assays, flow cytometry, RNA sequencing, and in vitro and in vivo models were used to uncover the biological functions and underlying mechanism of circZNF451 in LUAD anti-PD1 treatment resistance.
resultscircRNA sequencing and qRT-PCR identified the up-regulation of exosomal circZNF451 from LUAD patients with progressive disease (PD) compared to those with partial remission (PR) after PD1 blockade therapy. Furthermore, elevated circZNF451 was revealed to be associated with poor prognosis of LUAD patients. Additionally, exosomal circZNF451 was demonstrated to induce an anti-inflammatory phenotype in macrophages and exhaustion of cytotoxic CD8
conclusionExosomal circZNF451 reshapes the tumor immune microenvironment by inducing macrophages polarization via the FXR1- ELF4-IRF4 axis and is a novel biomarker for predicting the sensitivity of PD1 blockade in LUAD.
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