Department of Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, Province Guangdong, People's Republic of China.
Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing, 100029, China.
Cancer Immunol Immunother. 2024 Sep 5;73(11):217. doi: 10.1007/s00262-024-03807-1.
To provide molecular and immunological attributes mechanistic insights for the management of radiologically distinctive multiple primary lung cancer (MPLC).
The Bulk RNA-seq data of MPLC were obtained from our center. The Bulk RNA-seq data and CT images of patients with single primary lung cancer (SPLC) were obtained from GSE103584. Immune infiltration algorithms were performed to investigate the disparities in the immunological microenvironment between the two groups. Single-cell gene analysis was used to explore immune cells composition and communication relationships between cells in MPLC.
In MPLC, 11 pure ground-glass opacity nodules (pGGN) and 10 mixed GGN (mGGN) were identified, while in SPLC, the numbers were 18 pGGN and 22 mGGN, respectively. In MPLC, compared to pGGN, mGGN demonstrated a significantly elevated infiltration of CD8 T cells. Single-cell gene analysis demonstrated that CD8 T cells play a central role in the signaling among immune cells in MPLC. The transcription factors including MAFG, RUNX3, and TBX21 may play pivotal roles in regulation of CD8 T cells. Notably, compared to SPLC nodules for both mGGN and pGGN, MPLC nodules demonstrated a significantly elevated degree of tumor-infiltrating immune cells, with this difference being particularly pronounced in mGGN. There was a positive correlation between the proportion of immune cells and consolidation/tumor ratio (CTR).
Our findings provided a comprehensive description about the difference in the immune microenvironment between pGGN and mGGN in early-stage MPLC, as well as between MPLC and SPLC for both mGGN and pGGN. The findings may provide evidence for the design of immunotherapeutic strategies for MPLC.
为放射性特征明显的多原发性肺癌（MPLC）的管理提供分子和免疫学特征的机制见解。
从我们中心获得 MPLC 的 Bulk RNA-seq 数据。从 GSE103584 获得单发性原发性肺癌（SPLC）患者的 Bulk RNA-seq 数据和 CT 图像。进行免疫浸润算法以研究两组之间免疫微环境的差异。单细胞基因分析用于探索 MPLC 中免疫细胞组成和细胞间通讯关系。
在 MPLC 中，鉴定出 11 个纯磨玻璃影结节（pGGN）和 10 个混合 GGN（mGGN），而在 SPLC 中，pGGN 和 mGGN 的数量分别为 18 和 22。在 MPLC 中，与 pGGN 相比，mGGN 中 CD8+T 细胞浸润显著升高。单细胞基因分析表明，CD8+T 细胞在 MPLC 中免疫细胞间的信号传递中起核心作用。转录因子包括 MAFG、RUNX3 和 TBX21 可能在调节 CD8+T 细胞中发挥关键作用。值得注意的是，与 SPLC 结节的 mGGN 和 pGGN 相比，MPLC 结节中浸润的肿瘤免疫细胞程度显著升高，mGGN 中这种差异更为明显。免疫细胞的比例与实变/肿瘤比（CTR）呈正相关。
我们的研究结果全面描述了早期 MPLC 中 pGGN 和 mGGN 之间以及 mGGN 和 pGGN 的 MPLC 和 SPLC 之间免疫微环境的差异。这些发现可能为 MPLC 的免疫治疗策略设计提供依据。
