The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing
Abstract A thorough interrogation of the immune landscape is crucial for immunotherapy strategy selection and prediction of clinical responses in non-small-cell lung cancer (NSCLC) patients. Single-cell RNA sequencing (scRNA-seq) techniques have prompted the opportunity to dissect the distinct immun...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-08-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-022-01130-8 |
| _version_ | 1811188874769072128 |
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| author | Chengdi Wang Qiuxiao Yu Tingting Song Zhoufeng Wang Lujia Song Ying Yang Jun Shao Jingwei Li Yinyun Ni Ningning Chao Li Zhang Weimin Li |
| author_facet | Chengdi Wang Qiuxiao Yu Tingting Song Zhoufeng Wang Lujia Song Ying Yang Jun Shao Jingwei Li Yinyun Ni Ningning Chao Li Zhang Weimin Li |
| author_sort | Chengdi Wang |
| collection | DOAJ |
| description | Abstract A thorough interrogation of the immune landscape is crucial for immunotherapy strategy selection and prediction of clinical responses in non-small-cell lung cancer (NSCLC) patients. Single-cell RNA sequencing (scRNA-seq) techniques have prompted the opportunity to dissect the distinct immune signatures between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), the two major subtypes of NSCLC. Here, we performed scRNA-seq on 72,475 immune cells from 40 samples of tumor and matched adjacent normal tissues spanning 19 NSCLC patients, and drew a systematic immune cell transcriptome atlas. Joint analyses of the distinct cellular compositions, differentially expressed genes (DEGs), cell–cell interactions, pseudotime trajectory, transcriptomic factors and prognostic factors based on The Cancer Genome Atlas (TCGA), revealed the central roles of cytotoxic and effector T and NK cells and the distinct functional macrophages (Mφ) subtypes in the immune microenvironment heterogeneity between LUAD and LUSC. The dominant subtype of Mφ was FABP4-Mφ in LUAD and SPP1-Mφ in LUSC. Importantly, we identified a novel lymphocyte-related Mφ cluster, which we named SELENOP-Mφ, and further established its antitumor role in both types, especially in LUAD. Our comprehensive depiction of the immune heterogeneity and definition of Mφ clusters could help design personalized treatment for lung cancer patients in clinical practice. |
| first_indexed | 2024-04-11T14:26:24Z |
| format | Article |
| id | doaj.art-5367a3c4b18e4fab90c7c271877c538f |
| institution | Directory Open Access Journal |
| issn | 2059-3635 |
| language | English |
| last_indexed | 2024-04-11T14:26:24Z |
| publishDate | 2022-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj.art-5367a3c4b18e4fab90c7c271877c538f2022-12-22T04:18:51ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352022-08-017111710.1038/s41392-022-01130-8The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencingChengdi Wang0Qiuxiao Yu1Tingting Song2Zhoufeng Wang3Lujia Song4Ying Yang5Jun Shao6Jingwei Li7Yinyun Ni8Ningning Chao9Li Zhang10Weimin Li11Department of Respiratory and Critical Care Medicine, Med-X Center for Manufacturing, Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, West China Medical School, Sichuan UniversityNational Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Respiratory and Critical Care Medicine, Med-X Center for Manufacturing, Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, West China Medical School, Sichuan UniversityDepartment of Respiratory and Critical Care Medicine, Med-X Center for Manufacturing, Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, West China Medical School, Sichuan UniversityDepartment of Respiratory and Critical Care Medicine, Med-X Center for Manufacturing, Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, West China Medical School, Sichuan UniversityDepartment of Respiratory and Critical Care Medicine, Med-X Center for Manufacturing, Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, West China Medical School, Sichuan UniversityDepartment of Respiratory and Critical Care Medicine, Med-X Center for Manufacturing, Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, West China Medical School, Sichuan UniversityDepartment of Respiratory and Critical Care Medicine, Med-X Center for Manufacturing, Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, West China Medical School, Sichuan UniversityDepartment of Respiratory and Critical Care Medicine, Med-X Center for Manufacturing, Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, West China Medical School, Sichuan UniversityDepartment of Respiratory and Critical Care Medicine, Med-X Center for Manufacturing, Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, West China Medical School, Sichuan UniversityDepartment of Respiratory and Critical Care Medicine, Med-X Center for Manufacturing, Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, West China Medical School, Sichuan UniversityDepartment of Respiratory and Critical Care Medicine, Med-X Center for Manufacturing, Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, West China Medical School, Sichuan UniversityAbstract A thorough interrogation of the immune landscape is crucial for immunotherapy strategy selection and prediction of clinical responses in non-small-cell lung cancer (NSCLC) patients. Single-cell RNA sequencing (scRNA-seq) techniques have prompted the opportunity to dissect the distinct immune signatures between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), the two major subtypes of NSCLC. Here, we performed scRNA-seq on 72,475 immune cells from 40 samples of tumor and matched adjacent normal tissues spanning 19 NSCLC patients, and drew a systematic immune cell transcriptome atlas. Joint analyses of the distinct cellular compositions, differentially expressed genes (DEGs), cell–cell interactions, pseudotime trajectory, transcriptomic factors and prognostic factors based on The Cancer Genome Atlas (TCGA), revealed the central roles of cytotoxic and effector T and NK cells and the distinct functional macrophages (Mφ) subtypes in the immune microenvironment heterogeneity between LUAD and LUSC. The dominant subtype of Mφ was FABP4-Mφ in LUAD and SPP1-Mφ in LUSC. Importantly, we identified a novel lymphocyte-related Mφ cluster, which we named SELENOP-Mφ, and further established its antitumor role in both types, especially in LUAD. Our comprehensive depiction of the immune heterogeneity and definition of Mφ clusters could help design personalized treatment for lung cancer patients in clinical practice.https://doi.org/10.1038/s41392-022-01130-8 |
| spellingShingle | Chengdi Wang Qiuxiao Yu Tingting Song Zhoufeng Wang Lujia Song Ying Yang Jun Shao Jingwei Li Yinyun Ni Ningning Chao Li Zhang Weimin Li The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing Signal Transduction and Targeted Therapy |
| title | The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing |
| title_full | The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing |
| title_fullStr | The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing |
| title_full_unstemmed | The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing |
| title_short | The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing |
| title_sort | heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single cell rna sequencing |
| url | https://doi.org/10.1038/s41392-022-01130-8 |
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