Related Experiment Video
Updated: May 7, 2026

Native Chromatin Immunoprecipitation Using Murine Brain Tumor Neurospheres
Published on: January 29, 2018
Immune infiltration is associated with distinct transcriptional states and metabolic profiles in chordomas
Siddh van Oost1,2, Rick Ursem1,3, Zeynep B Erdem1,2
1Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
Abstract:
Chordomas are ultra-rare malignancies of the axial skeleton with limited treatment options. Some tumors exhibit immunogenic features and respond to checkpoint blockade, but the biological determinants remain unclear. To investigate chordoma immunogenicity, we integrated spatial transcriptomic and metabolomic profiling. GeoMx digital spatial profiling was performed on 15 chordomas, analyzing tumor and stromal compartments and comparing inflamed versus non-inflamed tumors. Consecutive sections underwent MALDI mass spectrometry imaging. Key findings were validated by immunohistochemistry. To link transcriptional states with interferon-γ, chordoma cell lines were treated with interferon-γ. Spatial profiling revealed transcriptomic differences between inflamed and non-inflamed tumors across both compartments, and immune infiltration correlated with a broader gene expression repertoire in cancer cells. MSI identified distinct metabolic signatures, including glycogen accumulation in inflamed tumors. However, interferon-γ treatment did not induce TBXT (brachyury) expression in chordoma cells. Together, these data reveal strong associations between transcriptional states, metabolic profiles, and immune infiltration in chordomas.
Insights
This study reveals that inflamed chordomas, a rare bone cancer, show distinct gene expression and metabolic profiles, including glycogen accumulation. These findings link tumor characteristics to immune infiltration, offering insights into potential immunotherapies.
Area of Science:
- Oncology
- Immunology
- Metabolomics
Background:
- Chordomas are rare axial skeleton cancers with few treatment options.
- Understanding chordoma immunogenicity is crucial for developing effective therapies, as some tumors respond to checkpoint blockade.
Purpose of the Study:
- To investigate the biological determinants of chordoma immunogenicity.
- To integrate spatial transcriptomic and metabolomic data to understand tumor-immune interactions.
Main Methods:
- Spatial transcriptomic profiling (GeoMx) and metabolomic imaging (MALDI-MSI) on 15 chordomas.
- Analysis of tumor and stromal compartments, comparing inflamed versus non-inflamed tumors.
- Validation by immunohistochemistry and interferon-γ treatment of chordoma cell lines.
Main Results:
- Inflamed chordomas showed distinct transcriptomic profiles in both tumor and stromal compartments.
- Immune infiltration correlated with a broader gene expression repertoire in cancer cells.
- Distinct metabolic signatures, including glycogen accumulation, were identified in inflamed tumors; interferon-γ did not induce brachyury (TBXT) expression.
Conclusions:
- Chordoma immunogenicity is associated with specific transcriptional states and metabolic profiles.
- These findings highlight the interplay between tumor biology and the immune microenvironment.
- The study provides a foundation for exploring novel immunotherapeutic strategies for chordoma.
More Related Videos
10:41An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues
Published on: April 5, 2018
11:50Genome-Wide Mapping of Histone Modifications and Transcription Factor Binding Sites in Neuroendocrine Small Cell Lung Cancer Cell Lines Using CUT&RUN
Published on: April 3, 2026
Related Concept Videos
Chronic Inflammation: Introduction
Chromatin Modification in iPS Cells
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Chromatin Immunoprecipitation- ChIP
Types of ChIP
ChIP can be divided into two types - X-ChIP and N-ChIP. X-ChIP involves in vivo cross-linking of histones and regulatory proteins to DNA, fragmenting the DNA by sonication, and isolating the protein-DNA...
Epigenetic Regulation
X-chromosome...
Chromatin Position Affects Gene Expression
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...