Genomic characteristics and immune landscape of super multiple primary lung cancer

Yang, Zhenlin; Zhou, Bolun; Guo, Wei; Peng, Yue; Tian, He; Xu, Jiachen; Wang, Shuaibo; Chen, Xiaowei; Hu, Bin; Liu, Chengming; Wang, Zhijie; Li, Chunxiang; Gao, Shugeng; He, Jie

doi:10.1016/j.ebiom.2024.105019

eBioMedicine

2024

DOI: 10.1016/j.ebiom.2024.105019

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Genomic characteristics and immune landscape of super multiple primary lung cancer

Zhenlin Yang,

Bolun Zhou,

Wei Guo

et al.

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2024

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Cited by 4 publications

References 52 publications

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Clonal expansion of shared T cell receptors reveals the existence of immune commonality among different lesions of synchronous multiple primary lung cancer

Wang,

Huang,

et al. 2024

Cancer Immunol Immunother

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The increase in the detection rate of synchronous multiple primary lung cancer (MPLC) has posed remarkable clinical challenges due to the limited understanding of its pathogenesis and molecular features. Here, comprehensive comparisons of genomic and immunologic features between MPLC and solitary lung cancer nodule (SN), as well as different lesions of the same patient, were performed. Compared with SN, MPLC displayed a lower rate of EGFR mutation but higher rates of BRAF, MAP2K1, and MTOR mutation, which function exactly in the upstream and downstream of the same signaling pathway. Considerable heterogeneity in T cell receptor (TCR) repertoire exists among not only different patients but also among different lesions of the same patient. Invasive lesions of MPLC exhibited significantly higher TCR diversity and lower TCR expansion than those of SN. Intriguingly, different lesions of the same patient always shared a certain proportion of TCR clonotypes. Significant clonal expansion could be observed in shared TCR clonotypes, particularly in those existing in all lesions of the same patient. In conclusion, this study provided evidences of the distinctive mutational landscape, activation of oncogenic signaling pathways, and TCR repertoire in MPLC as compared with SN. The significant clonal expansion of shared TCR clonotypes demonstrated the existence of immune commonality among different lesions of the same patient and shed new light on the individually tailored precision therapy for MPLC.

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Clonal expansion of shared T cell receptors reveals the existence of immune commonality among different lesions of synchronous multiple primary lung cancer

Wang,

Huang,

et al. 2024

Cancer Immunol Immunother

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Confronting synchronous multiple primary lung cancers: Navigating the intersection of challenges and opportunities

He,

Yang,

et al. 2024

Lung Cancer

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Super multiple primary lung cancers harbor high-frequency BRAF and low-frequency EGFR mutations in the MAPK pathway

Li,

Huang,

Guo

et al. 2024

npj Precis. Onc.

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The incidence of multiple primary lung cancer (MPLC) is increasing, with some of our surgical patients exhibiting numerous lesions. We defined lung cancer with five or more primary lesions as super MPLCs. Elucidating the genomic characteristics of this special MPLC subtype can help reduce disease burden and understand tumor evolution. In our cohort of synchronous super early-stage MPLCs (PUMCH-ssesMPLC), whole-exome sequencing on 130 resected malignant specimens from 18 patients provided comprehensive super-MPLC genomic landscapes. Mutations are enriched in PI3k-Akt and MAPK pathways. Their BRAF mutation frequency (31.5%) is significantly higher than MPLC with fewer lesions and early-stage single-lesion cancer, while EGFR mutations are significantly fewer (13.8%). As lesion counts increase, BRAF mutations gradually become dominant. Also, invasive lesions more tend to have classic super-MPLC mutation patterns. High-frequency BRAF mutations, especially Class II, and low-frequency EGFR mutations could be a reason for the limited effectiveness of targeted therapy in super-MPLC patients.

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Genomic characteristics and immune landscape of super multiple primary lung cancer

Cited by 4 publications

References 52 publications

Clonal expansion of shared T cell receptors reveals the existence of immune commonality among different lesions of synchronous multiple primary lung cancer

Clonal expansion of shared T cell receptors reveals the existence of immune commonality among different lesions of synchronous multiple primary lung cancer

Confronting synchronous multiple primary lung cancers: Navigating the intersection of challenges and opportunities

Super multiple primary lung cancers harbor high-frequency BRAF and low-frequency EGFR mutations in the MAPK pathway

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