Multi-omics profiling reveals tumor microenvironment characteristics linked to immunotherapy response and prognosis in non-small cell lung cancer
Blocking a tumor-signaling protein restored immune cell function and boosted immunotherapy effectiveness in resistant lung cancer models.
Integrating 31 datasets, this study found that ZNF683+ CD8+ T cells are enriched in anti-PD-1 responders and that a ZNFRS risk score predicts prognosis in lung adenocarcinoma; high-risk tumors showed an immunosuppressive TME driven by SPP1 signaling. Anti-SPP1 treatment in mouse models restored CD8+ T cell function and enhanced anti-PD-1 efficacy, identifying a potential combination strategy for immunotherapy-resistant NSCLC.
What the study was
- Study design
- Integrative bioinformatics (31 datasets) with in vivo validation in mouse models
- Population
- NSCLC patients (multi-dataset analysis); mouse models for in vivo validation
- Category
- Genomics/Precision Medicine
- Maturity
- Exploratory
- Journal
- NPJ Precision Oncology
Why it surfaced
Comprehensive multi-dataset bioinformatics (31 datasets) + in vivo validation of anti-SPP1 + anti-PD-1 combination in NSCLC. ZNF683 as immunotherapy biomarker is novel. Score capped at 7 due to primary evidence being retrospective/bioinformatics without prospective human clinical validation; mouse in vivo is encouraging but insufficient to elevate to HIGH.
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