Comparative immunological landscape between pre- and early-stage LUAD manifested as ground-glass nodules revealed by scRNA and scTCR integrated analysis
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 preca...
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-023-01322-x |
| _version_ | 1797557757520379904 |
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| author | Ziqi Wang Li Yang Wenqiang Wang Huanhuan Zhou Juan Chen Zeheng Ma Xiaoyan Wang Quncheng Zhang Haiyang Liu Chao Zhou Zhiping Guo Xiaoju Zhang |
| author_facet | Ziqi Wang Li Yang Wenqiang Wang Huanhuan Zhou Juan Chen Zeheng Ma Xiaoyan Wang Quncheng Zhang Haiyang Liu Chao Zhou Zhiping Guo Xiaoju Zhang |
| author_sort | Ziqi Wang |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-03-10T17:20:55Z |
| format | Article |
| id | doaj.art-e88e2b3fd5fb435ab10d4e0c8b07ef18 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-03-10T17:20:55Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-e88e2b3fd5fb435ab10d4e0c8b07ef182023-11-20T10:21:47ZengBMCCell Communication and Signaling1478-811X2023-11-0121112410.1186/s12964-023-01322-xComparative immunological landscape between pre- and early-stage LUAD manifested as ground-glass nodules revealed by scRNA and scTCR integrated analysisZiqi Wang0Li Yang1Wenqiang Wang2Huanhuan Zhou3Juan Chen4Zeheng Ma5Xiaoyan Wang6Quncheng Zhang7Haiyang Liu8Chao Zhou9Zhiping Guo10Xiaoju Zhang11Department of Respiratory and Critical Care Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s HospitalDepartment of Respiratory and Critical Care Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s HospitalDepartment of Respiratory and Critical Care Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s HospitalDepartment of Respiratory and Critical Care Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s HospitalDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Thoracic Surgery Department, Zhengzhou University People’s Hospital, Henan Provincial People’s HospitalDepartment of Pathological Department, Zhengzhou University People’s Hospital, Henan Provincial People’s HospitalDepartment of Respiratory and Critical Care Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s HospitalDepartment of Respiratory and Critical Care Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s HospitalDepartment of Respiratory and Critical Care Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s HospitalZhengzhou University People’s Hospital, Henan Provincial People’s HospitalDepartment of Respiratory and Critical Care Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s HospitalAbstract 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 Abstracthttps://doi.org/10.1186/s12964-023-01322-xGround glass noduleLung adenocarcinomascRNA-seqScTCR-seqTumor microenvironment |
| spellingShingle | Ziqi Wang Li Yang Wenqiang Wang Huanhuan Zhou Juan Chen Zeheng Ma Xiaoyan Wang Quncheng Zhang Haiyang Liu Chao Zhou Zhiping Guo Xiaoju Zhang Comparative immunological landscape between pre- and early-stage LUAD manifested as ground-glass nodules revealed by scRNA and scTCR integrated analysis Cell Communication and Signaling Ground glass nodule Lung adenocarcinoma scRNA-seq ScTCR-seq Tumor microenvironment |
| title | Comparative immunological landscape between pre- and early-stage LUAD manifested as ground-glass nodules revealed by scRNA and scTCR integrated analysis |
| title_full | Comparative immunological landscape between pre- and early-stage LUAD manifested as ground-glass nodules revealed by scRNA and scTCR integrated analysis |
| title_fullStr | Comparative immunological landscape between pre- and early-stage LUAD manifested as ground-glass nodules revealed by scRNA and scTCR integrated analysis |
| title_full_unstemmed | Comparative immunological landscape between pre- and early-stage LUAD manifested as ground-glass nodules revealed by scRNA and scTCR integrated analysis |
| title_short | Comparative immunological landscape between pre- and early-stage LUAD manifested as ground-glass nodules revealed by scRNA and scTCR integrated analysis |
| title_sort | comparative immunological landscape between pre and early stage luad manifested as ground glass nodules revealed by scrna and sctcr integrated analysis |
| topic | Ground glass nodule Lung adenocarcinoma scRNA-seq ScTCR-seq Tumor microenvironment |
| url | https://doi.org/10.1186/s12964-023-01322-x |
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