Dissecting the single-cell transcriptome network underlying thymic neuroendocrine tumor and thymus non-malignant tissues (A14)

Introduction: Thymic neuroendocrine tumor (TNET) is the rarest subtype among thymic epithelial tumors and NET. Limited understanding of tumor microenvironment (TME) of TNET contributes to the lack of treatment options for this rare tumor type.

Aim(s): We aim to conduct a comprehensive analysis of the TME in TNET and to explore potential pathogenesis and therapeutic targets for TNET.

Materials and methods: We performed single-cell RNA sequencing (scRNA) analysis on three tumor specimens and their corresponding non-tumor tissues. Additionally, scRNA data of normal thymic neuroendocrine (NE) cells were retrieved from publicly available databases.

Results: After quality filtering, 38,602 cells underwent analysis, categorized into seven subgroups revealing a notable deficiency of T&NK cells within the tumor. Trajectory analysis and functional scoring revealed an abundance of naive CD8+ T cells within the tumor, while dendritic cells and macrophages exhibited no significant differences between tumors and non-tumor tissues. Comparative analysis between tumor and normal NE cells highlighted upregulated pathways related to cell proliferation and angiogenesis in tumor cells, alongside a downregulation of antigen presentation and immune-related pathways. Transitioning from normal fibroblasts (NF) to tumor-associated fibroblasts (CAF) demonstrated an upregulation of pathways related to immune regulation and vascular endothelial cell differentiation.

Conclusion: The TME in TNET exhibits immune suppression and a heightened proliferative state in tumor cells. The interplay between tumor cells, immune cells and CAF potentially holds a pivotal role in driving these traits.

Keywords: thymic neuroendocrine tumor, single-cell rna sequencing, tumor microenvironment, tumor-associated fibroblasts