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The spatial transcriptomic landscape of non-small cell lung cancer brain metastasis

Author

Listed:
  • Qi Zhang

    (Western University)

  • Rober Abdo

    (Western University
    Western University)

  • Cristiana Iosef

    (Western University
    Children’s Health Research Institute)

  • Tomonori Kaneko

    (Western University)

  • Matthew Cecchini

    (Western University)

  • Victor K. Han

    (Children’s Health Research Institute)

  • Shawn Shun-Cheng Li

    (Western University
    Children’s Health Research Institute)

Abstract

Brain metastases (BrMs) are a common occurrence in lung cancer with a dismal outcome. To understand the mechanism of metastasis to inform prognosis and treatment, here we analyze primary and metastasized tumor specimens from 44 non-small cell lung cancer patients by spatial RNA sequencing, affording a whole transcriptome map of metastasis resolved with morphological markers for the tumor core, tumor immune microenvironment (TIME), and tumor brain microenvironment (TBME). Our data indicate that the tumor microenvironment (TME) in the brain, including the TIME and TBME, undergoes extensive remodeling to create an immunosuppressive and fibrogenic niche for the BrMs. Specifically, the brain TME is characterized with reduced antigen presentation and B/T cell function, increased neutrophils and M2-type macrophages, immature microglia, and reactive astrocytes. Differential gene expression and network analysis identify fibrosis and immune regulation as the major functional modules disrupted in both the lung and brain TME. Besides providing systems-level insights into the mechanism of lung cancer brain metastasis, our study uncovers potential prognostic biomarkers and suggests that therapeutic strategies should be tailored to the immune and fibrosis status of the BrMs.

Suggested Citation

  • Qi Zhang & Rober Abdo & Cristiana Iosef & Tomonori Kaneko & Matthew Cecchini & Victor K. Han & Shawn Shun-Cheng Li, 2022. "The spatial transcriptomic landscape of non-small cell lung cancer brain metastasis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33365-y
    DOI: 10.1038/s41467-022-33365-y
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    as
    1. Patrick Danaher & Youngmi Kim & Brenn Nelson & Maddy Griswold & Zhi Yang & Erin Piazza & Joseph M. Beechem, 2022. "Advances in mixed cell deconvolution enable quantification of cell types in spatial transcriptomic data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. David O. Dias & Jannis Kalkitsas & Yildiz Kelahmetoglu & Cynthia P. Estrada & Jemal Tatarishvili & Daniel Holl & Linda Jansson & Shervin Banitalebi & Mahmood Amiry-Moghaddam & Aurélie Ernst & Hagen B., 2021. "Pericyte-derived fibrotic scarring is conserved across diverse central nervous system lesions," Nature Communications, Nature, vol. 12(1), pages 1-24, December.
    3. Michael Tyler & Itay Tirosh, 2021. "Decoupling epithelial-mesenchymal transitions from stromal profiles by integrative expression analysis," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    4. David H. Peng & Bertha Leticia Rodriguez & Lixia Diao & Limo Chen & Jing Wang & Lauren A. Byers & Ying Wei & Harold A. Chapman & Mitsuo Yamauchi & Carmen Behrens & Gabriela Raso & Luisa Maren Solis So, 2020. "Collagen promotes anti-PD-1/PD-L1 resistance in cancer through LAIR1-dependent CD8+ T cell exhaustion," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    5. Giulia E. Tyzack & Sergey Sitnikov & Daniel Barson & Kerala L. Adams-Carr & Nike K. Lau & Jessica C. Kwok & Chao Zhao & Robin J. M. Franklin & Ragnhildur T. Karadottir & James W. Fawcett & András Laka, 2014. "Astrocyte response to motor neuron injury promotes structural synaptic plasticity via STAT3-regulated TSP-1 expression," Nature Communications, Nature, vol. 5(1), pages 1-15, September.
    6. Peter A. Szabo & Hanna Mendes Levitin & Michelle Miron & Mark E. Snyder & Takashi Senda & Jinzhou Yuan & Yim Ling Cheng & Erin C. Bush & Pranay Dogra & Puspa Thapa & Donna L. Farber & Peter A. Sims, 2019. "Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    7. Nayoung Kim & Hong Kwan Kim & Kyungjong Lee & Yourae Hong & Jong Ho Cho & Jung Won Choi & Jung-Il Lee & Yeon-Lim Suh & Bo Mi Ku & Hye Hyeon Eum & Soyean Choi & Yoon-La Choi & Je-Gun Joung & Woong-Yang, 2020. "Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    8. Dieter Henrik Heiland & Vidhya M. Ravi & Simon P. Behringer & Jan Hendrik Frenking & Julian Wurm & Kevin Joseph & Nicklas W. C. Garrelfs & Jakob Strähle & Sabrina Heynckes & Jürgen Grauvogel & Pamela , 2019. "Tumor-associated reactive astrocytes aid the evolution of immunosuppressive environment in glioblastoma," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
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    1. Anna Skakodub & Henry Walch & Kathryn R. Tringale & Jordan Eichholz & Brandon S. Imber & Harish N. Vasudevan & Bob T. Li & Nelson S. Moss & Kenny Kwok Hei Yu & Boris A. Mueller & Simon Powell & Pedram, 2023. "Genomic analysis and clinical correlations of non-small cell lung cancer brain metastasis," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Chengdi Wang & Jingwei Li & Jingyao Chen & Zhoufeng Wang & Guonian Zhu & Lujia Song & Jiayang Wu & Changshu Li & Rong Qiu & Xuelan Chen & Li Zhang & Weimin Li, 2025. "Multi-omics analyses reveal biological and clinical insights in recurrent stage I non-small cell lung cancer," Nature Communications, Nature, vol. 16(1), pages 1-19, December.

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