Single-cell and spatial transcriptomics profile the interaction of SPP1+ macrophages and FAP+ fibroblasts in non-small cell lung cancer
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View abstract on PubMed
Summary
This summary is machine-generated.We identified that higher SPP1 expression in non-small cell lung cancer (NSCLC) macrophages interacts with FAP+ fibroblasts, forming a barrier that hinders anti-cancer immunity and reduces immunotherapy effectiveness.
Area Of Science
- Oncology
- Immunology
- Genomics
Background
- Non-small cell lung cancer (NSCLC) is a prevalent malignancy.
- Differentially expressed genes (DEGs) in tumor microenvironments (TME) are crucial for tumor biology.
- Understanding TME-related DEGs in NSCLC is essential.
Purpose Of The Study
- To systematically investigate TME-related DEGs in NSCLC.
- To elucidate the mechanisms of functional DEGs in NSCLC tumor biology.
Main Methods
- Compared bulk transcriptomes of adjacent and tumor NSCLC samples across 7 cohorts.
- Annotated DEG expression patterns to specific cell types using scRNA-seq data from 13 NSCLC studies.
- Validated spatial interactions using immunofluorescence and spatial transcriptomics (ST), and functional relevance via mouse models.
Main Results
- Identified 82 overlapping DEGs, with SPP1 being the top DEG, specifically expressed in myeloid cells (macrophages).
- SPP1+ macrophages interact with FAP+ fibroblasts, forming an immune-excluding barrier.
- Macrophage-specific Spp1 knockout in mice reduced tumor size and increased T cell infiltration; high FAP/SPP1 expression correlated with poor immunotherapy prognosis.
Conclusions
- SPP1+ macrophages and FAP+ fibroblasts interact in NSCLC, creating a barrier that impedes immune infiltration.
- This interaction reduces immunotherapy efficacy in NSCLC patients.
- Targeting SPP1-FAP interactions may enhance immunotherapy outcomes.
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