Nature Communications (Sep 2024)
Genomic and immune heterogeneity of multiple synchronous lung adenocarcinoma at different developmental stages
- Yue Zhao,
- Jian Gao,
- Jun Wang,
- Fanfan Fan,
- Chao Cheng,
- Danwen Qian,
- Ran Guo,
- Yang Zhang,
- Ting Ye,
- Marcellus Augustine,
- Yicong Lin,
- Jun Shang,
- Hang Li,
- Yunjian Pan,
- Qingyuan Huang,
- Haiqing Chen,
- Han Han,
- Zhendong Gao,
- Qiming Wang,
- Shiyue Zhang,
- Mou Zhang,
- Fangqiu Fu,
- Yueren Yan,
- Shanila Fernandez Patel,
- Roberto Vendramin,
- Hui Yuan,
- Yawei Zhang,
- Jiaqing Xiang,
- Hong Hu,
- Yihua Sun,
- Yuan Li,
- Kevin Litchfield,
- Zhiwei Cao,
- Haiquan Chen
Affiliations
- Yue Zhao
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Jian Gao
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Jun Wang
- School of Life Sciences, Fudan University
- Fanfan Fan
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Chao Cheng
- Department of Thoracic Surgery, West China Hospital of Sichuan University
- Danwen Qian
- Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute
- Ran Guo
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Yang Zhang
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Ting Ye
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Marcellus Augustine
- Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute
- Yicong Lin
- Department of Oncology, Shanghai Medical College, Fudan University
- Jun Shang
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Hang Li
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Yunjian Pan
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Qingyuan Huang
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Haiqing Chen
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Han Han
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Zhendong Gao
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Qiming Wang
- School of Life Sciences, Fudan University
- Shiyue Zhang
- School of Life Sciences, Fudan University
- Mou Zhang
- School of Life Sciences, Fudan University
- Fangqiu Fu
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Yueren Yan
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Shanila Fernandez Patel
- Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute
- Roberto Vendramin
- Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute
- Hui Yuan
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Yawei Zhang
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Jiaqing Xiang
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Hong Hu
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Yihua Sun
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- Yuan Li
- Department of Oncology, Shanghai Medical College, Fudan University
- Kevin Litchfield
- Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute
- Zhiwei Cao
- International Human Phenome Institutes (Shanghai)
- Haiquan Chen
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center
- DOI
- https://doi.org/10.1038/s41467-024-52139-2
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 14
Abstract
Abstract Multiple synchronous lung cancers (MSLCs) constitute a unique subtype of lung cancer. To explore the genomic and immune heterogeneity across different pathological stages of MSLCs, we analyse 16 MSLCs from 8 patients using single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing. Our investigation indicates clonally independent tumours with convergent evolution driven by shared driver mutations. However, tumours from the same individual exhibit few shared mutations, indicating independent origins. During the transition from pre-invasive to invasive adenocarcinoma, we observe a shift in T cell phenotypes characterized by increased Treg cells and exhausted CD8+ T cells, accompanied by diminished cytotoxicity. Additionally, invasive adenocarcinomas exhibit greater neoantigen abundance and a more diverse TCR repertoire, indicating heightened heterogeneity. In summary, despite having a common genetic background and environmental exposure, our study emphasizes the individuality of MSLCs at different stages, highlighting their unique genomic and immune characteristics.
