The single cell transcriptional landscape of fibrosarcoma.

235 Background: Fibrosarcoma (FS) is a relatively uncommon subtype of soft tissue sarcoma, which predominantly occurs in the extremities and girdles of elderly individuals. FS are famous for its high recurrence and metastasis rate. However, the current treatment regimens have shown poor efficacy in treating these progressive lesions. Therefore, a deep understanding of the tumor microenvironment characteristics of fibrosarcoma is needed to develop more effective drugs.Therefore, a deeper understanding of the tumor microenvironment characteristics of fibrosarcoma is needed for further development of therapeutic drugs. Methods: We performed single-cell transcriptome sequencing for the first time on 6 patients bearing with FS. Bulk-seq data of soft tissue sarcoma was downloaded from public database including TCGA and GEO for prognostic analysis. What' s more, a cohort of 54 FS patients was retrospectively collected for protein detection. Results: The tumor microenvironment landscape was characterized by the presence of malignant fibroblast, diverse macrophages, limited T-cell presence, and high levels of vascular infiltration. The expression of siglec15 was significantly upregulated in the malignant cells. And the prognostic significance of siglec15 was confirmed by the TCGA public database. What’s more, the high expression of siglec15 protein was negatively related to overall survival of fibrosarcoma patients from our institution. We also explored the interactions among different cell subtypes, especially the interactions between malignant cells and endothelial cells, as well as macrophages and endothelial cells, which not only promote tumor progression but also inhibit T-cell infiltration and function. Conclusions: In total, our work has uncovered the low T cell infiltration landscape of FS. The primary reason of insufficient immune infiltration may be due to the blockage of T cell extravasation caused by the interaction between endothelial cells, malignant cells and macrophages.