ArticleNeuro-oncology2026
Integrated immune profiling of chordomas reveals spatially organized niches and functional heterogeneity.
Article in Neuro-oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Immune infiltration is associated with distinct transcriptional states and metabolic profiles in chordomas.iScience · 2026Article
- Progression-free survival 3 of 22 months achieved through third-line therapy with adebrelimab in patient with recurrent chordoma: a case report.Frontiers in oncology · 2026Article
- Immunosuppressive mechanisms and therapeutic interventions shaping glioblastoma immunity.Nature cancer · 2026Review
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32 authors.
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Abstract
backgroundChordomas are locally aggressive notochordal tumors with no systemic therapy options. As an ultra-rare cancer type, our understanding of its immune landscape is limited. While tumor-associated macrophages (TAMs) and T cells are critical components of the immune landscape, their functional states and interactions remain poorly understood.
methodsWe conducted an integrative analysis of 35 chordoma samples and six paired tumor-PBMC samples using single-cell RNA sequencing (scRNA-seq), T-cell receptor (TCR) profiling, and multiplex immunofluorescence. Immune cell phenotypes, spatial distribution, TCR motif diversity, and functional states were assessed using unbiased co-expression network analysis and predictive modeling.
resultsChordomas exhibited remarkable immune cell heterogeneity, ranging from highly infiltrated to immune--desert tumors. Tumor-associated macrophages dominated the tumor microenvironment (TME) and were enriched for antigen-processing pathways. T-cell receptor profiling revealed clonal overlap between tumor-infiltrating and peripheral T cells, suggesting systemic anti-tumor responses. Exhausted CD8+ T cells exhibited restricted clonality and tumor-specific amino acid motifs. Weighted gene co-expression network analysis (WGCNA) identified gene modules associated with immune activation and suppression, underscoring the dual roles of immune cells in the TME. Spatial analysis revealed fibrous septa as immune interaction hubs, where immune cell clustering was significantly higher than in tumor regions.
conclusionsThis study advances understanding of the chordoma immune landscape by integrating spatial, transcriptomic, and TCR data. The findings highlight systemic and local immune dynamics, reveal tumor-specific TCR motifs, and identify potential therapeutic targets. These insights provide a foundation for developing personalized immunotherapies to overcome immune suppression and enhance anti-tumor immunity in chordomas.
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