1965P - Transcriptional analysis of immune microenvironment of chordomas of the skull base and mobile spine

Background

Chordomas are rare neoplasms of notochord origin that can affect the skull base and mobile spine. While surgery and radiation are effective means to treat localized disease, there are no standard systemic therapies to treat locally advanced/metastatic chordomas. We previously published a series of chordoma patients treated with immune checkpoint inhibitors demonstrating limited activity. Here we begin to evaluate the immune microenvironment of chordomas by transcriptional analysis.

Methods

57 tissue samples (30 spine chordoma, 21 skull base chordoma, 6 normal), previously analyzed by RNA-sequencing analysis and published (PMID: 28844110), were used. Hierarchical clustering was used to evaluate expression of immune-related genes. Gene ontology analysis was performed with GeneAnalytics. Microenvironment Cell Populations-counter (MCP-counter) was used for quantification of immune cell populations. Spearman’s rank correlation coefficient and t-tests were used for statistical purposes.

Results

Populations of endothelial cells were significantly different in skull base (SB) samples (p<0.05) and mobile spine (MS) samples (p<0.01) compared to normal. B cells were significantly different in MS compared to normal (p<0.05), and monocytes were significantly different in SB samples compared to normal (p<0.001). 19 genes of the Interferon gamma (IFNG) gene pathway were significantly altered (p<0.05) in SB samples compared to MS samples but only 4 genes of the IFNG pathway were significantly altered (p<0.05) in SB samples compared to normal samples. 9 genes of the IFNG pathway were significantly altered in MS samples compared to normal (p<0.05). Hierarchical clustering of immune-related gene expression revealed 3 distinct groups. Gene ontology analysis revealed that group 1 favored NF-kappa B signaling pathway, group 2 favored the phagosome pathway, and group 3 represented dendritic cell development lineage pathway.

Conclusions

Chordomas of the skull base and mobile spine exhibit diverse immune cell populations and differential expression of mediators of immune response. A comprehensive analysis is needed to further our understanding of the immune microenvironment of chordoma to develop ideal immunotherapeutic strategies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A.P. Conley: Other, Institutional, Research Funding, clinical trial support: Chordoma Foundation, Epicentrx; Other, Personal and Institutional, Research Funding, clinical trial support; consulting: Inhibrx; Financial Interests, Personal, Advisory Board, consulting: Aadi Biosciences. All other authors have declared no conflicts of interest.