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 () and Haiquan Chen ()
Additional contact information
Yue Zhao: Fudan University Shanghai Cancer Center
Jian Gao: Fudan University Shanghai Cancer Center
Jun Wang: Fudan University
Fanfan Fan: Fudan University Shanghai Cancer Center
Chao Cheng: West China Hospital of Sichuan University
Danwen Qian: University College London Cancer Institute
Ran Guo: Fudan University Shanghai Cancer Center
Yang Zhang: Fudan University Shanghai Cancer Center
Ting Ye: Fudan University Shanghai Cancer Center
Marcellus Augustine: University College London Cancer Institute
Yicong Lin: Fudan University
Jun Shang: Fudan University Shanghai Cancer Center
Hang Li: Fudan University Shanghai Cancer Center
Yunjian Pan: Fudan University Shanghai Cancer Center
Qingyuan Huang: Fudan University Shanghai Cancer Center
Haiqing Chen: Fudan University Shanghai Cancer Center
Han Han: Fudan University Shanghai Cancer Center
Zhendong Gao: Fudan University Shanghai Cancer Center
Qiming Wang: Fudan University
Shiyue Zhang: Fudan University
Mou Zhang: Fudan University
Fangqiu Fu: Fudan University Shanghai Cancer Center
Yueren Yan: Fudan University Shanghai Cancer Center
Shanila Fernandez Patel: University College London Cancer Institute
Roberto Vendramin: University College London Cancer Institute
Hui Yuan: Fudan University Shanghai Cancer Center
Yawei Zhang: Fudan University Shanghai Cancer Center
Jiaqing Xiang: Fudan University Shanghai Cancer Center
Hong Hu: Fudan University Shanghai Cancer Center
Yihua Sun: Fudan University Shanghai Cancer Center
Yuan Li: Fudan University
Kevin Litchfield: University College London Cancer Institute
Zhiwei Cao: International Human Phenome Institutes (Shanghai)
Haiquan Chen: Fudan University Shanghai Cancer Center

Nature Communications, 2024, vol. 15, issue 1, 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.

Date: 2024
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DOI: 10.1038/s41467-024-52139-2

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