IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33365-y.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33365-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-33365-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    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. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    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.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Osama Al-Dalahmah & Michael G. Argenziano & Adithya Kannan & Aayushi Mahajan & Julia Furnari & Fahad Paryani & Deborah Boyett & Akshay Save & Nelson Humala & Fatima Khan & Juncheng Li & Hong Lu & Yu S, 2023. "Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Xianhui Ruan & Wei Yan & Minghui Cao & Ray Anthony M. Daza & Miranda Y. Fong & Kaifu Yang & Jun Wu & Xuxiang Liu & Melanie Palomares & Xiwei Wu & Arthur Li & Yuan Chen & Rahul Jandial & Nicholas C. Sp, 2024. "Breast cancer cell-secreted miR-199b-5p hijacks neurometabolic coupling to promote brain metastasis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Magnus Zethoven & Luciano Martelotto & Andrew Pattison & Blake Bowen & Shiva Balachander & Aidan Flynn & Fernando J. Rossello & Annette Hogg & Julie A. Miller & Zdenek Frysak & Sean Grimmond & Lauren , 2022. "Single-nuclei and bulk-tissue gene-expression analysis of pheochromocytoma and paraganglioma links disease subtypes with tumor microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    4. Xiaojian Lu & Yanwei Luo & Xichen Nie & Bailing Zhang & Xiaoyan Wang & Ran Li & Guangmin Liu & Qianyin Zhou & Zhizhong Liu & Liqing Fan & James M. Hotaling & Zhe Zhang & Hao Bo & Jingtao Guo, 2023. "Single-cell multi-omics analysis of human testicular germ cell tumor reveals its molecular features and microenvironment," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Felix Drost & Yang An & Irene Bonafonte-Pardàs & Lisa M. Dratva & Rik G. H. Lindeboom & Muzlifah Haniffa & Sarah A. Teichmann & Fabian Theis & Mohammad Lotfollahi & Benjamin Schubert, 2024. "Multi-modal generative modeling for joint analysis of single-cell T cell receptor and gene expression data," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    6. Haoyang Li & Juexiao Zhou & Zhongxiao Li & Siyuan Chen & Xingyu Liao & Bin Zhang & Ruochi Zhang & Yu Wang & Shiwei Sun & Xin Gao, 2023. "A comprehensive benchmarking with practical guidelines for cellular deconvolution of spatial transcriptomics," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    7. Ioana Olan & Masami Ando-Kuri & Aled J. Parry & Tetsuya Handa & Stefan Schoenfelder & Peter Fraser & Yasuyuki Ohkawa & Hiroshi Kimura & Masako Narita & Masashi Narita, 2024. "HMGA1 orchestrates chromatin compartmentalization and sequesters genes into 3D networks coordinating senescence heterogeneity," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    8. Han Luo & Xuyang Xia & Li-Bin Huang & Hyunsu An & Minyuan Cao & Gyeong Dae Kim & Hai-Ning Chen & Wei-Han Zhang & Yang Shu & Xiangyu Kong & Zhixiang Ren & Pei-Heng Li & Yang Liu & Huairong Tang & Rongh, 2022. "Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    9. Jeff DeMartino & Michael T. Meister & Lindy L. Visser & Mariël Brok & Marian J. A. Groot Koerkamp & Amber K. L. Wezenaar & Laura S. Hiemcke-Jiwa & Terezinha Souza & Johannes H. M. Merks & Anne C. Rios, 2023. "Single-cell transcriptomics reveals immune suppression and cell states predictive of patient outcomes in rhabdomyosarcoma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    10. Yuna Landais & Céline Vallot, 2023. "Multi-modal quantification of pathway activity with MAYA," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    11. Michael Papanicolaou & Amelia L. Parker & Michelle Yam & Elysse C. Filipe & Sunny Z. Wu & Jessica L. Chitty & Kaitlin Wyllie & Emmi Tran & Ellie Mok & Audrey Nadalini & Joanna N. Skhinas & Morghan C. , 2022. "Temporal profiling of the breast tumour microenvironment reveals collagen XII as a driver of metastasis," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    12. Augusto Faria Andrade & Alva Annett & Elham Karimi & Danai Georgia Topouza & Morteza Rezanejad & Yitong Liu & Michael McNicholas & Eduardo G. Gonzalez Santiago & Dhana Llivichuzhca-Loja & Arne Gehlhaa, 2024. "Immune landscape of oncohistone-mutant gliomas reveals diverse myeloid populations and tumor-promoting function," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    13. Mathias Linnerbauer & Tobias Beyer & Lucy Nirschl & Daniel Farrenkopf & Lena Lößlein & Oliver Vandrey & Anne Peter & Thanos Tsaktanis & Hania Kebir & David Laplaud & Rupert Oellinger & Thomas Engleitn, 2023. "PD-L1 positive astrocytes attenuate inflammatory functions of PD-1 positive microglia in models of autoimmune neuroinflammation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    14. Yang Zhang & Gan Liu & Minzhen Tao & Hui Ning & Wei Guo & Gaofei Yin & Wen Gao & Lifei Feng & Jin Gu & Zhen Xie & Zhigang Huang, 2023. "Integrated transcriptome study of the tumor microenvironment for treatment response prediction in male predominant hypopharyngeal carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    15. Gregor Werba & Daniel Weissinger & Emily A. Kawaler & Ende Zhao & Despoina Kalfakakou & Surajit Dhara & Lidong Wang & Heather B. Lim & Grace Oh & Xiaohong Jing & Nina Beri & Lauren Khanna & Tamas Gond, 2023. "Single-cell RNA sequencing reveals the effects of chemotherapy on human pancreatic adenocarcinoma and its tumor microenvironment," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    16. Chunman Zuo & Yijian Zhang & Chen Cao & Jinwang Feng & Mingqi Jiao & Luonan Chen, 2022. "Elucidating tumor heterogeneity from spatially resolved transcriptomics data by multi-view graph collaborative learning," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    17. Thomas M. Goralski & Lindsay Meyerdirk & Libby Breton & Laura Brasseur & Kevin Kurgat & Daniella DeWeerd & Lisa Turner & Katelyn Becker & Marie Adams & Daniel J. Newhouse & Michael X. Henderson, 2024. "Spatial transcriptomics reveals molecular dysfunction associated with cortical Lewy pathology," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    18. Hai C. T. Nguyen & Bukyung Baik & Sora Yoon & Taesung Park & Dougu Nam, 2023. "Benchmarking integration of single-cell differential expression," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    19. Nader Atlasy & Anna Bujko & Espen S. Bækkevold & Peter Brazda & Eva Janssen-Megens & Knut E. A. Lundin & Jørgen Jahnsen & Frode L. Jahnsen & Hendrik G. Stunnenberg, 2022. "Single cell transcriptomic analysis of the immune cell compartment in the human small intestine and in Celiac disease," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    20. Stefanie Hiltbrunner & Lena Cords & Sabrina Kasser & Sandra N. Freiberger & Susanne Kreutzer & Nora C. Toussaint & Linda Grob & Isabelle Opitz & Michael Messerli & Martin Zoche & Alex Soltermann & Mar, 2023. "Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33365-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.