Single-Cell RNA Sequencing Unravels Distinct Tumor Microenvironment of Different Components of Lung Adenocarcinoma Featured as Mixed Ground-Glass Opacity

Frontiers in Immunology

Xiaofeng Chen¹  Yi Tian²  Fenglei Yu³  Muyun Peng³  Qikang Hu³  Bin Wang³  Li Wang³  Yongguang Tao³  Yu He³  Yan Hu³ 

[1] Department of Anaesthesia, The Second Xiangya Hospital of Central South University, Changsha, China;Department of Thoracic Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China;Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, China;

关键词: ground-glass opacity;    non-small cell lung cancer;    intra-tumor heterogeneity;    single-cell RNA sequencing;    macrophage;   

DOI  :  10.3389/fimmu.2022.903513

来源: DOAJ

【 摘 要 】

Lung adenocarcinoma featured as mixed ground-glass opacity (mGGO) doubled its volume half of the time in comparison with that featured as pure ground-glass opacity (pGGO). The mechanisms underlying the heterogeneous appearance of mGGO remain elusive. In this study, we macro-dissected the solid (S) components and ground-glass (GG) components of mGGO and performed single-cell sequencing analyses of six paired components from three mGGO patients. A total of 19,391 single-cell profiles were taken into analysis, and the data of each patient were analyzed independently to obtain a common alteration. Cancer cells and macrophages were the dominant cell types in the S and GG components, respectively. Cancer cells in the S components, which showed relatively malignant phenotypes, were likely to originate from both the GG and S components and monitor the surrounding tumor microenvironment (TME) through an intricate cell interaction network. SPP1hi macrophages were enriched in the S components and showed increased activity of chemoattraction, while macrophages in the GG components displayed an active antimicrobial process with a higher stress-induced state. In addition, the CD47–SIRPA axis was demonstrated to be critical in the maintenance of the GG components. Taken together, our study unraveled the alterations of cell components and transcriptomic features between different components in mGGOs.

【 授权许可】

Unknown