دورية أكاديمية

Comparative immunological landscape between pre- and early-stage LUAD manifested as ground-glass nodules revealed by scRNA and scTCR integrated analysis

التفاصيل البيبلوغرافية
العنوان: Comparative immunological landscape between pre- and early-stage LUAD manifested as ground-glass nodules revealed by scRNA and scTCR integrated analysis
المؤلفون: Ziqi Wang, Li Yang, Wenqiang Wang, Huanhuan Zhou, Juan Chen, Zeheng Ma, Xiaoyan Wang, Quncheng Zhang, Haiyang Liu, Chao Zhou, Zhiping Guo, Xiaoju Zhang
المصدر: Cell Communication and Signaling, Vol 21, Iss 1, Pp 1-24 (2023)
بيانات النشر: BMC, 2023.
سنة النشر: 2023
المجموعة: LCC:Medicine
LCC:Cytology
مصطلحات موضوعية: Ground glass nodule, Lung adenocarcinoma, scRNA-seq, ScTCR-seq, Tumor microenvironment, Medicine, Cytology, QH573-671
الوصف: Abstract Background Mechanism underlying the malignant progression of precancer to early-stage lung adenocarcinoma (LUAD) as well as their indolence nature remains elusive. Methods Single-cell RNA sequencing (scRNA) with simultaneous T cell receptor (TCR) sequencing on 5 normal lung tissues, 3 precancerous and 4 early-stage LUAD manifested as pulmonary ground-glass nodules (GGNs) were performed. Results Through this integrated analysis, we have delineated five key modules that drive the malignant progression of early-stage LUAD in a disease stage-dependent manner. These modules are related to cell proliferation and metabolism, immune response, mitochondria, cilia, and cell adhesion. We also find that the tumor micro-environment (TME) of early-stage LUAD manifested as GGN are featured with regulatory T (Tregs) cells accumulation with three possible origins, and loss-functional state (decreased clonal expansion and cytotoxicity) of CD8 + T cells. Instead of exhaustion, the CD8 + T cells are featured with a shift to memory phenotype, which is significantly different from the late stage LUAD. Furthermore, we have identified monocyte-derived macrophages that undergo a lipid-phenotype transition and may contribute to the suppressive TME. Intense interaction between stromal cells, myeloid cells including lipid associated macrophages and LAMP3 + DCs, and lymphocytes were also characterized. Conclusions Our work provides new insight into the molecular and cellular mechanism underlying malignant progression of LUAD manifested as GGN, and pave way for novel immunotherapies for GGN. Video Abstract
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1478-811X
Relation: https://doaj.org/toc/1478-811X
DOI: 10.1186/s12964-023-01322-x
URL الوصول: https://doaj.org/article/e88e2b3fd5fb435ab10d4e0c8b07ef18
رقم الأكسشن: edsdoj.88e2b3fd5fb435ab10d4e0c8b07ef18
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:1478811X
DOI:10.1186/s12964-023-01322-x