ArticleCancer immunology, immunotherapy : CII2023
PLEK2 and IFI6, representing mesenchymal and immune-suppressive microenvironment, predicts resistance to neoadjuvant immunotherapy in esophageal squamous cell carcinoma.
Article in Cancer immunology, immunotherapy : CII, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 18 citations in OpenAlex.
- Integrating tumor and immune cell transcriptomics to predict immune checkpoint inhibitor primary resistance in metastatic melanoma.Oncoimmunology · 2026Article
- Integrated spatial and single-cell transcriptomics uncover IFI6⁺ regulatory T-cells and SPP1⁺ macrophages immunosuppressive niches in colorectal cancer.British journal of cancer · 2026Article
- IGF2-associated tumor cells and APOE-positive macrophages define an imatinib resistance-associated niche in gastrointestinal stromal tumors.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- RBM15 Contributes to Bladder Carcinoma Progression via m6A-dependent Stabilization of IFI6 mRNA.Applied biochemistry and biotechnology · 2026Article
- A novel programmed-cell-death-related prognostic risk model for cervical cancer based on mitochondrial genes.Translational cancer research · 2026Article
- Synergistic NIR-polydopamine nanotherapy for blood-brain barrier crossing and Parkinson's disease intervention.RSC advances · 2026Article
- Pan cohort immune biomarker of CD8 lymphocyte activation enabling HGSOC outcome prediction and treatment response.Discover oncology · 2025Article
- Unmasking immune checkpoint resistance in esophageal squamous cell carcinoma: Insights into the tumor microenvironment and biomarker landscape.World journal of gastrointestinal oncology · 2025Review
- Uncovering gene and cellular signatures of immune checkpoint response via machine learning and single-cell RNA-seq.NPJ precision oncology · 2025Article
- A transformer-based deep learning survival prediction model and an explainable XGBoost anti-PD-1/PD-L1 outcome prediction model based on the cGAS-STING-centered pathways in hepatocellular carcinoma.Briefings in bioinformatics · 2024Article
- Unveiling the role of Pleckstrin-2 in tumor progression and immune modulation: insights from a comprehensive pan-cancer analysis with focus on lung cancer.Molecular biomedicine · 2024Article
- Spatial multiomics of arterial regions from cardiac allograft vasculopathy rejected grafts reveal novel insights into the pathogenesis of chronic antibody-mediated rejection.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2024Article
- Effect of cervical paraesophageal lymph node metastasis versus supraclavicular lymph node metastasis on the overall survival of patients with thoracic esophageal squamous cell carcinoma: an observational study.Annals of medicine and surgery (2012) · 2024Article
- Multi-Omics Analysis Reveals the IFI6 Gene as a Prognostic Indicator and Therapeutic Target in Esophageal Cancer.International journal of molecular sciences · 2024Article
- Developing and validating the model of tumor-infiltrating immune cell to predict survival in patients receiving radiation therapy for head and neck squamous cell carcinoma.Translational cancer research · 2024Article
- From tumor microenvironment to emerging biomarkers: the reshaping of the esophageal squamous cell carcinoma tumor microenvironment by neoadjuvant chemotherapy combined with immunotherapy.Frontiers in immunology · 2024Review
- COL19A1 is a predictive biomarker for the responsiveness of esophageal squamous cell carcinoma patients to immune checkpoint therapy.Thoracic cancer · 2023Article
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundImmunotherapy has largely improved clinical outcome of patients with esophageal squamous cell carcinoma (ESCC). However, a proportion of patients still fail to benefit. Thus, biomarkers predicting therapeutic resistance and underlying mechanism needs to be investigated.
methodsTranscriptomic profiling was applied in FFPE tissues from 103 ESCC patients, including surgical samples from 66 treatment-naïve patients with long-term follow-up, and endoscopic biopsies from 37 local advanced ESCC cases receiving neoadjuvant immunotherapy plus chemotherapy. Unsupervised clustering indicated an aggressive phenotype with mesenchymal character in 66 treatment-naïve samples. Univariant logistic regression was applied to identify candidate biomarkers potentially predicted resistance to neoadjuvant immunotherapy within the range of mesenchymal phenotype enriched genes. These biomarkers were further validated by immunohistochemistry. Putative mechanisms mediating immunotherapy resistance, as indicated by microenvironment and immune cell infiltration, were evaluated by transcriptomic data, and validated by multiplex immunofluorescence.
resultsPLEK2 and IFI6, highly expressed in mesenchymal phenotype, were identified as novel biomarkers relating to non-MPR in neoadjuvant immunotherapy cohort [PLEK2
conclusionsPLEK2 and IFI6 was discovered of first time to identify a distinct ESCC subpopulation cannot be benefited from neoadjuvant immunotherapy and present a poor survival, which putatively associated with mesenchymal and immune-suppressive microenvironment.
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