Abstract B017: Characterizing the key stromal and immune players in the microenvironment of primary and metastatic chordoma
Authors: Jackett Kailey , Sowder Miranda , John Liny , Hazelwood Ignatius , Kaplan Rosandra 
Published: January 2023

Chordoma is a rare bone sarcoma of the skull and spine with notochordal origins and an incidence of approximately 1 in every 1,000,000 people. Most chordomas (95%) are pathologically classified as conventional type and generally affect adults. Other chordoma subtypes include dedifferentiated and poorly differentiated with the latter being more common in pediatric patients and both being more aggressive with higher propensity for metastasis than conventional chordomas. Depending on the subtype, local recurrence and metastasis occurs in ~40-80% and ~5-40% of patients, respectively. Due to the rarity of this cancer, the understanding of primary and metastatic chordoma and its microenvironment is poor. Consequently, there are currently no standard therapies for recurrent or metastatic chordomas and 10-year survival rates remain around 30%. The tumor microenvironment (TME), a cellular ecosystem composed of nonmalignant cells that can promote tumor development and progression, offers a promising perspective that could yield novel insights into metastatic chordoma. Stromal and immune cells play key roles in tumor initiation, dissemination, metastasis, and therapeutic response. We hypothesize that the progression of cancer is intimately linked to the characteristics of immune and myeloid populations within the TME. Despite significant advances in the understanding of the genomic landscape of chordoma, the complex cellular milieu of the chordoma TME and its contribution to tumor progression remains unclear. To understand the prevalence and diversity of stromal and immune cells within the chordoma TME, we are utilizing multiplex immunofluorescence on a tissue microarray of chordomas (n=~30). Our preliminary findings show that tumor cell (brachyury+) contribution to the TME is highly heterogenous ranging from 2-88% (SD = 20.0, avg = 30%). Further, stromal cells (aSMA+) are the predominant cell type, comprised ~40% of the TME (SD = 19, 8-78%) whereas CD11b+ myeloid cells were rare contributing only to ~0.15% (SD = 0.39, 0-1.6%) of the cellular milieu in the chordoma TME. These results indicate a high degree of heterogeneity in stromal and myeloid cell populations between chordoma tumors and further our understanding of the spatial relationship between TME populations and tumor cells. Ongoing studies will include stromal cell subtyping (pericytes, endothelial cells, etc) and investigation of other immune populations including T cells and macrophages by multiplex immunofluorescence. Additionally, these immune- and stromal-rich regions will serve as regions of interest for future spatial transcriptomics studies. Further analysis of stromal and immune subsets within the TME of chordoma could reveal insights into mechanisms of metastasis and tumor progression, with the hope for additional treatment options to effectively re-educate the TME to eliminate tumor cells as well as identify key tumorigenic cell populations.

Citation Format: Kailey Jackett, Miranda Sowder, Liny John, Ignatius Hazelwood, Rosandra Kaplan. Characterizing the key stromal and immune players in the microenvironment of primary and metastatic chordoma [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr B017.