Genomic and immune heterogeneity of multiple synchronous lung adenocarcinoma at different developmental stages
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<sup>+</sup> 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.
Authors
- Fanfan Fan (ORCID: https://orcid.org/0009-0002-0898-5054)
- Kevin Litchfield (ORCID: https://orcid.org/0000-0002-3725-0914)
- Hui Yuan (ORCID: https://orcid.org/0000-0001-9739-3645)
- Roberto Vendramin (ORCID: https://orcid.org/0000-0001-7191-4887)
- Mou Zhang (ORCID: https://orcid.org/0000-0002-6941-7985)
- Ran Guo (ORCID: https://orcid.org/0000-0003-0167-128X)
- Marcellus Augustine
- Jiaqing Xiang (ORCID: https://orcid.org/0000-0001-9636-2150)
- Danwen Qian (ORCID: https://orcid.org/0000-0002-6209-0764)
- Chao Cheng (ORCID: https://orcid.org/0000-0003-3571-8154)
- Shiyue Zhang (ORCID: https://orcid.org/0009-0001-5313-9802)
- Yicong Lin (ORCID: https://orcid.org/0000-0002-3994-4637)
- Fangqiu Fu (ORCID: https://orcid.org/0000-0001-5791-4741)
- Jun Shang (ORCID: https://orcid.org/0000-0002-5767-1492)
- Yueren Yan (ORCID: https://orcid.org/0000-0002-2826-2251)
- Jian Gao (ORCID: https://orcid.org/0000-0002-0446-7471)
- Yunjian Pan (ORCID: https://orcid.org/0000-0002-6117-8385)
- Qingyuan Huang (ORCID: https://orcid.org/0000-0003-4389-6188)
- Han Han (ORCID: https://orcid.org/0000-0003-2222-5270)
- Yang Zhang (ORCID: https://orcid.org/0000-0002-0098-8974)
- Jun Wang (ORCID: https://orcid.org/0009-0005-4877-0930)
- Qiming Wang (ORCID: https://orcid.org/0000-0003-3217-1077)
- Yue Zhao (ORCID: https://orcid.org/0000-0003-3645-2634)
- Ting Ye (ORCID: https://orcid.org/0000-0002-5704-400X)
- Haiquan Chen (ORCID: https://orcid.org/0000-0001-7846-257X)
- Yihua Sun (ORCID: https://orcid.org/0000-0002-5287-0601)
- Hong Hu (ORCID: https://orcid.org/0000-0003-3497-0454)
- Zhiwei Cao (ORCID: https://orcid.org/0000-0003-1165-1928)
- Yuan Li (ORCID: https://orcid.org/0000-0001-9338-2463)
- Haiqing Chen (ORCID: https://orcid.org/0009-0009-4555-9362)
- Zhendong Gao (ORCID: https://orcid.org/0000-0002-8816-2543)
- Shanila Fernandez Patel
- Yawei Zhang
- Hang Li (ORCID: https://orcid.org/0000-0001-8612-9451)
Institutions
- Shanghai Medical College of Fudan University (CN)
- Sichuan University (CN)
- Fudan University (CN)
- Cancer Research UK (GB)
- London Cancer (GB)
- West China Hospital of Sichuan University (CN)
- Fudan University Shanghai Cancer Center (CN)
- Shanghai Institutes for International Studies (CN)
- CRUK Lung Cancer Centre of Excellence (GB)
- University College London (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-10
- DOI
- https://doi.org/10.1038/s41467-024-52139-2
- Citations
- 12
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 3.42
Funders
- National Natural Science Foundation of China
- Fudan University