基于单细胞测序的多发性肺癌细胞组成和免疫特性研究

多发性肺癌的精确诊治是目前尚未得到共识性解决方案的难题，对其细胞组成和免疫特性的深入研究是改善临床现状的关键。前期研究中我们进行单细胞测序解析了多发性肺癌的细胞构成，描述了病灶间共性与异质性，初步探索了肿瘤免疫微环境的生物学特性，并注册和建立了多发性肺癌前瞻性临床队列。本项目将进一步基于单细胞测序和空间转录组学分析揭示多发性肺癌的细胞组成和免疫微环境，阐明各细胞之间的分子作用，明确肿瘤细胞特异性反应与病人临床、病理、影像学、分子信息之间的关系，测试其对肺癌预后和免疫治疗的预测价值。这些研究将增加我们对多发性肺癌多细胞生态系统的生物学理解，揭示其细胞结构和免疫特性，为推动临床上多发性肺癌的精准诊疗提供重要的理论基础。

Multiple synchronous lung cancer (MSLC) is diagnosed as multiple tumor nodules in the same or different lung lobes, and is a frequent occurrence in individuals with lung cancer. However, the cellular architecture and immune characteristics for the synchronous tumors remain largely unclear in most patients. We have sequenced a unique cohort of MSLC using single-cell RNA sequencing to investigate cellular composition, identify the similarity and heterogeneity for the synchronous tumors, and reveal the characteristics of immune cells in MSLC. Based on these findings, we propose this project to further expand our samples into a large prospective MSLC cohort. We will further apply single-cell RNA sequencing and spatial transcriptomics to dissect the multicellular ecosystem of MSLC, investigate cell-cell interactions and explore the correlations between tumor response and specific clinical factors. These studies will improve our understanding of MSLC biology and reveal the cellular architecture underlying the development of MSLC.