A Circulating GPNMB-Based Multimodal Model Integrates Tumor-Immune Crosstalk to Predict Immunotherapy Response in Esophageal Cancer - PubMed
4 hours ago
- #immunotherapy
- #ESCC
- #biomarker
- Neoadjuvant immunotherapy improves outcomes in esophageal squamous cell carcinoma (ESCC), but ~70% of patients do not respond.
- Plasma proteomic profiling identified soluble glycoprotein non-metastatic melanoma protein B (sGPNMB) as highly elevated in non-responders.
- sGPNMB suppresses CD8+ T cell receptor (TCR) signaling via the SDC4-CD148 axis, leading to T cell exhaustion.
- Cancer-associated fibroblast-epithelial (CAF-Epi) niches promote SOX2 upregulation in tumor cells, which transcriptionally activates GPNMB expression.
- Circulating GPNMB levels predicted response to PD-1 blockade in humanized PDX models, and GPNMB inhibition synergized with therapy.
- A multimodal model combining plasma GPNMB levels, CAF-Epi niche detection, and clinical-pathological features accurately predicted immunotherapy response and survival.