背景:鼻咽癌(NPC)是一种明显的恶性肿瘤,其潜在机制部分被理解,敦促进一步研究其多样化和动态的肿瘤微环境(TME),以支持诊断,治疗,和预后的准确性。
目的:为了追踪转移的进化途径,在这里,我们执行了来自24个原发癌的scRNA-seq数据,7外周血单个核细胞(PBMC)鼻咽癌,和7名转移癌患者的样本。
方法:在高质量控制和过滤之后,来自这些肿瘤的总共292,298个细胞被分为10个簇:T细胞,B细胞,巨噬细胞/单核细胞,自然杀伤(NK)细胞,浆细胞,浆细胞样树突状细胞,迁移树突状细胞,肥大细胞,与癌症相关的成纤维细胞,和上皮细胞。
结果:通过比较和分析原发性和转移性鼻咽癌中细胞实体的不同功能,加上对T细胞异质性和命运差异轨迹的详细研究,B细胞,和骨髓细胞,以及评估这些致癌状态之间的细胞间传播异质性的相互作用,我们建立了原发性和转移性肿瘤的单细胞图谱,并确定了大量潜在的治疗靶点.
结论:这项综合分析通过在单细胞分辨率下详细说明肿瘤微环境的进化动力学和影响,显著提高了我们对鼻咽癌(NPC)转移的理解。从而为未来的转移性肿瘤研究奠定了关键的基础,并为免疫异质性提供了新的见解,分子相互作用,以及NPC的潜在治疗策略。
BACKGROUND: Nasopharyngeal carcinoma (NPC) is an assertive malignancy with partially understood underlying mechanisms, urging further study into its diverse and dynamic tumor microenvironment (TME) to bolster diagnosis, treatment, and prognostic accuracy.
OBJECTIVE: To track the evolutionary route of metastasis, here we perform a yielding scRNA-seq data from 24 primary carcinoma, 7 peripheral blood mononuclear cell (PBMC) nasopharyngeal carcinoma, and 7 metastatic carcinoma patients\' sample.
METHODS: Following high quality control and filtration, a total of 292,298 cells from these tumors were classified into 10 clusters: T cells, B cells, Macrophages/Monocytes, Natural Killer (NK) cells, Plasma cells, plasmacytoid Dendritic Cells, Migratory Dendritic Cells, Mast cells, Cancer-Associated Fibroblasts, and Epithelial cells.
RESULTS: By comparing and analyzing the different functional capacities of cellular entities within primary and metastatic nasopharyngeal carcinoma, coupled with a detailed investigation into the heterogeneity and differential fate trajectories of T cells, B cells, and myeloid cells, as well as assessing the interactions of cell-cell communicative heterogeneity between these carcinogenic states, we established single-cell atlases for primary and metastatic tumors and identified a large number of potential therapeutic targets.
CONCLUSIONS: This comprehensive analysis significantly advances our understanding of nasopharyngeal carcinoma (NPC) metastasis by detailing the evolutionary dynamics and the impact of the tumor microenvironment at a single-cell resolution, thereby laying a crucial foundation for future metastatic tumor research and providing new insights into immune heterogeneity, molecular interactions, and potential therapeutic strategies for NPC.