IGHG1+ malignant epithelial Cell-myCAF crosstalk via MIF-CD74/APP-CD74 drives early brain metastasis in NSCLC: Delineated via primary tumor-brain metastasis single-cell and spatial transcriptomics - P
5 hours ago
- #CD74 targeting
- #brain metastasis
- #NSCLC
- The study investigates early brain metastasis mechanisms in NSCLC using spatial multi-omics, focusing on IGHG1+ malignant epithelial cells (MECs) and myCAFs.
- IGHG1+ MECs are enriched at the invasive front of primary tumors with brain metastasis, co-localizing with myCAFs, and show strong EMT pathway enrichment.
- Bidirectional crosstalk between IGHG1+ MECs and myCAFs occurs via MIF-CD74/APP-CD74 axes, identified as key drivers of brain metastasis in NSCLC.
- High CD74 expression at tumor margins independently predicts brain metastasis (AUC = 0.776) and is associated with shorter brain metastasis-free survival (37 vs 60 months).
- Potential therapeutic targets like doxorubicin and milatuzumab, which inhibit EMT by targeting CD74, show promise in preclinical models for preventing brain metastasis.