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.

Iscience
|May 6, 2026
PubMed

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.

Related Concept Videos

Chronic Inflammation: Introduction01:12

Chronic Inflammation: Introduction

Chronic inflammation is a prolonged, dysregulated immune response that persists for weeks to years when the inciting stimulus is difficult to eradicate or when self‑antigens drive ongoing reactivity. Morphologically, it is defined by mononuclear cell infiltration, progressive tissue destruction, and concurrent attempts at healing via angiogenesis and fibrosis. Compared with acute inflammation, edema is less prominent while cellular infiltration predominates; triggers include persistent...
51
Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (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...
1.5K
Chromatin Immunoprecipitation- ChIP02:36

Chromatin Immunoprecipitation- ChIP

Chromatin immunoprecipitation, or ChIP, is an antibody-based technique used to identify sites on DNA that bind to transcription factors of interest or histone proteins. It also helps determine the type of histone modifications such as acetylation, phosphorylation, or methylation.
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...
9.5K
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
3.5K
Chromatin Position Affects Gene Expression02:35

Chromatin Position Affects Gene Expression

Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
22.5K