运用单细胞转录组测序刻画食管鳞癌微环境细胞图谱并探索趋化因子CCL19对食管鳞癌放化疗敏感性的影响

新辅助放化疗联合手术是治疗局部晚期食管鳞癌的重要模式。然而，新辅助放化疗疗效存在异质性，由食管鳞癌微环境中的肿瘤细胞和非肿瘤细胞群体的异质性共同决定。我们首次对接受新辅助放化疗的放化疗前、后食管鳞癌组织进行单细胞转录组测序，证实了食管鳞癌组织的复杂细胞构成，并发现一系列在不同放化疗敏感性组织中存在显著差异表达的基因，如趋化因子CCL19等。本研究中，我们将进一步对前期获得的单细胞转录组测序数据进行深度分析，从单细胞水平层面阐明食管鳞癌微环境的细胞异质性构成及放化疗对其的动态影响，探索各种细胞间可能存在的相互作用；寻找新辅助放化疗疗效相关的细胞亚群与基因表达；通过体内外实验验证并探索趋化因子CCL19及其受体CCR7对食管鳞癌组织微环境中免疫细胞的趋化作用进而影响放化疗敏感性的机制。本项目将有助于深刻解析食管鳞癌异质性的细胞和分子基础，对食管鳞癌个体化精准治疗具有重要的理论与临床实践意义。

Neoadjuvant chemoradiotherapy (neo-CRT) is an important strategy for advanced esophageal squamous cell carcinoma (ESCC) treatment. However, responses to neo-CRT are heterogeneous, determined by the heterogeneities of both tumor and non-tumor cells in the ESCC tumor microenvironment. We conducted the single-cell RNA sequencing on ESCC samples acquired before and after neo-CRT, which demonstrated the complex cell constitution of ESCC tissues and identified a series of genes differentially expressed between ESCCs of different neo-CRT response, such as chemokine CCL19. In the current study, we are going to further explore the single-cell RNA sequencing data of ESCC tissues, elucidate the heterogeneous cell components of ESCC tumor microenvironment, the effect of CRT on them and their interplay at the single cell level; identify the cell population and gene expression related to neo-CRT response; explore the chemotaxis of chemokine CCL19 and its receptor CCR7 on immune cells, and thereby effects on ESCC neo-CRT sensitivity and underlying mechanisms. This study would aid in deep understanding of the cellular and molecular bases of ESCC heterogeneity, and lay foundation for precision treatment of ESCC.