随着早期诊断的进步，越来越多的多原发性肺癌（MPLC）患者被发现。然而，MPLC的进展涉及细胞组成和代谢功能的复杂变化，这仍然存在很大争议。我们的研究旨在全面揭示MPLC的细胞特征和细胞间连接。我们对6名MPLC患者的23个样本进行了scRNA-seq ，与批量全外显子组测序相结合。我们进行了轨迹分析，以研究 MPLC 发展过程中不同细胞类型的转变。对来自 MPLC 患者肿瘤和邻近组织的总共 1 67 397 个细胞进行了测序，并鉴定了肿瘤细胞、正常细胞、免疫细胞和基质细胞。确定了上皮细胞的两种状态，分别与免疫反应和细胞死亡相关。此外，CD8 幼稚 T 细胞和记忆 T 细胞都参与了 CD8 T 细胞的分化。 CD8 T 细胞的终末状态是耗尽的 T 细胞和细胞毒性 T 细胞，它们分别正向调节细胞死亡并参与细胞因子产生的调节。鉴定出具有不同功能的两个主要 B 细胞亚群，它们分别参与免疫反应和抗原呈递的调节。此外，我们发现一种特定类型的内皮细胞在肿瘤样本中丰富，并且从正常样本到肿瘤样本呈增加趋势。我们的研究展示了MPLC不同细胞的综合景观，这可能揭示关键的细胞机制，因此，可能为 MPLC 的早期诊断和治疗提供新的见解。© 2023 作者。约翰·威利出版的《临床与转化医学》

With the advancements in early diagnosis, more and more patients with multiple primary lung cancer (MPLC) have been identified. However, the progression of MPLC involves complex changes in cell composition and metabolic function, which remains largely controversial.Our study aims to comprehensively reveal the cellular characteristics and inter-cellular connections of MPLC.We performed scRNA-seq from 23 samples of six MPLC patients, combined with bulk whole-exome sequencing. We performed trajectory analysis to investigate the transition of different cell types during the development of MPLC.A total of 1 67 397 cells were sequenced derived from tumour and adjacent tissues of MPLC patients, and tumour, normal, immune and stromal cells were identified. Two states of epithelial cells were identified, which were associated with immune response and cell death, respectively. Furthermore, both CD8+ naïve and memory T cells participated in the differentiation of CD8+ T cells. The terminal states of CD8+ T cells were exhausted T cells and cytotoxic T cells, which positively regulated cell death and were implicated in the regulation of cytokine production, respectively. Two main subpopulations of B cells with distinct functions were identified, which participate in the regulation of the immune response and antigen presentation, respectively. In addition, we found a specific type of endothelial cells that were abundant in tumour samples, with an increasing trend from normal to tumour samples.Our study showed the comprehensive landscape of different cells of MPLC, which might reveal the key cellular mechanisms and, therefore, may provide new insights into the early diagnosis and treatment of MPLC.© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.