IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-49595-1.html
   My bibliography  Save this article

Immuno-oncologic profiling of pediatric brain tumors reveals major clinical significance of the tumor immune microenvironment

Author

Listed:
  • Adrian B. Levine

    (The Hospital for Sick Children
    University of Toronto
    The Hospital for Sick Children
    University of British Columbia)

  • Liana Nobre

    (University of Toronto
    University of Alberta)

  • Anirban Das

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Scott Milos

    (The Hospital for Sick Children)

  • Vanessa Bianchi

    (The Hospital for Sick Children)

  • Monique Johnson

    (The Hospital for Sick Children)

  • Nicholas R. Fernandez

    (The Hospital for Sick Children)

  • Lucie Stengs

    (The Hospital for Sick Children)

  • Scott Ryall

    (The Hospital for Sick Children
    University of Toronto)

  • Michelle Ku

    (The Hospital for Sick Children)

  • Mansuba Rana

    (The Hospital for Sick Children)

  • Benjamin Laxer

    (The Hospital for Sick Children)

  • Javal Sheth

    (The Hospital for Sick Children)

  • Stefanie-Grace Sbergio

    (The Hospital for Sick Children
    University of Toronto)

  • Ivana Fedoráková

    (University Children’s Hospital)

  • Vijay Ramaswamy

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Julie Bennett

    (The Hospital for Sick Children
    The Hospital for Sick Children
    Princess Margaret Cancer Centre)

  • Robert Siddaway

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Uri Tabori

    (The Hospital for Sick Children
    University of Toronto
    The Hospital for Sick Children)

  • Cynthia Hawkins

    (The Hospital for Sick Children
    University of Toronto
    The Hospital for Sick Children)

Abstract

With the success of immunotherapy in cancer, understanding the tumor immune microenvironment (TIME) has become increasingly important; however in pediatric brain tumors this remains poorly characterized. Accordingly, we developed a clinical immune-oncology gene expression assay and used it to profile a diverse range of 1382 samples with detailed clinical and molecular annotation. In low-grade gliomas we identify distinct patterns of immune activation with prognostic significance in BRAF V600E-mutant tumors. In high-grade gliomas, we observe immune activation and T-cell infiltrates in tumors that have historically been considered immune cold, as well as genomic correlates of inflammation levels. In mismatch repair deficient high-grade gliomas, we find that high tumor inflammation signature is a significant predictor of response to immune checkpoint inhibition, and demonstrate the potential for multimodal biomarkers to improve treatment stratification. Importantly, while overall patterns of immune activation are observed for histologically and genetically defined tumor types, there is significant variability within each entity, indicating that the TIME must be evaluated as an independent feature from diagnosis. In sum, in addition to the histology and molecular profile, this work underscores the importance of reporting on the TIME as an essential axis of cancer diagnosis in the era of personalized medicine.

Suggested Citation

  • Adrian B. Levine & Liana Nobre & Anirban Das & Scott Milos & Vanessa Bianchi & Monique Johnson & Nicholas R. Fernandez & Lucie Stengs & Scott Ryall & Michelle Ku & Mansuba Rana & Benjamin Laxer & Java, 2024. "Immuno-oncologic profiling of pediatric brain tumors reveals major clinical significance of the tumor immune microenvironment," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49595-1
    DOI: 10.1038/s41467-024-49595-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-49595-1
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-49595-1?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. Francisco Avila Cobos & José Alquicira-Hernandez & Joseph E. Powell & Pieter Mestdagh & Katleen De Preter, 2020. "Benchmarking of cell type deconvolution pipelines for transcriptomics data," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    2. Robert Siddaway & Scott Milos & Arun Kumaran Anguraj Vadivel & Tara H. W. Dobson & Jyothishmathi Swaminathan & Scott Ryall & Sanja Pajovic & Palak G. Patel & Javad Nazarian & Oren Becher & Michael Bru, 2022. "Splicing is an alternate oncogenic pathway activation mechanism in glioma," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Michael Schubert & Bertram Klinger & Martina Klünemann & Anja Sieber & Florian Uhlitz & Sascha Sauer & Mathew J. Garnett & Nils Blüthgen & Julio Saez-Rodriguez, 2018. "Perturbation-response genes reveal signaling footprints in cancer gene expression," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    4. Francisco Avila Cobos & José Alquicira-Hernandez & Joseph E. Powell & Pieter Mestdagh & Katleen Preter, 2020. "Author Correction: Benchmarking of cell type deconvolution pipelines for transcriptomics data," Nature Communications, Nature, vol. 11(1), pages 1-1, December.
    5. Sanja Pajovic & Robert Siddaway & Taylor Bridge & Javal Sheth & Patricia Rakopoulos & Byungjin Kim & Scott Ryall & Sameer Agnihotri & Lauren Phillips & Man Yu & Christopher Li & Scott Milos & Palak Pa, 2020. "Epigenetic activation of a RAS/MYC axis in H3.3K27M-driven cancer," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    Full references (including those not matched with items on IDEAS)

    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. Kobe Ridder & Huiwen Che & Kaat Leroy & Bernard Thienpont, 2024. "Benchmarking of methods for DNA methylome deconvolution," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Nelson Johansen & Hongru Hu & Gerald Quon, 2023. "Projecting RNA measurements onto single cell atlases to extract cell type-specific expression profiles using scProjection," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Kang Wang & Ioannis Zerdes & Henrik J. Johansson & Dhifaf Sarhan & Yizhe Sun & Dimitris C. Kanellis & Emmanouil G. Sifakis & Artur Mezheyeuski & Xingrong Liu & Niklas Loman & Ingrid Hedenfalk & Jonas , 2024. "Longitudinal molecular profiling elucidates immunometabolism dynamics in breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    4. Eloise Berson & Anjali Sreenivas & Thanaphong Phongpreecha & Amalia Perna & Fiorella C. Grandi & Lei Xue & Neal G. Ravindra & Neelufar Payrovnaziri & Samson Mataraso & Yeasul Kim & Camilo Espinosa & A, 2023. "Whole genome deconvolution unveils Alzheimer’s resilient epigenetic signature," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    5. Yann Vanrobaeys & Zeru J. Peterson & Emily. N. Walsh & Snehajyoti Chatterjee & Li-Chun Lin & Lisa C. Lyons & Thomas Nickl-Jockschat & Ted Abel, 2023. "Spatial transcriptomics reveals unique gene expression changes in different brain regions after sleep deprivation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Khoa A. Tran & Venkateswar Addala & Rebecca L. Johnston & David Lovell & Andrew Bradley & Lambros T. Koufariotis & Scott Wood & Sunny Z. Wu & Daniel Roden & Ghamdan Al-Eryani & Alexander Swarbrick & E, 2023. "Performance of tumour microenvironment deconvolution methods in breast cancer using single-cell simulated bulk mixtures," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Gavin J. Sutton & Daniel Poppe & Rebecca K. Simmons & Kieran Walsh & Urwah Nawaz & Ryan Lister & Johann A. Gagnon-Bartsch & Irina Voineagu, 2022. "Comprehensive evaluation of deconvolution methods for human brain gene expression," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    8. Daniel Charytonowicz & Rachel Brody & Robert Sebra, 2023. "Interpretable and context-free deconvolution of multi-scale whole transcriptomic data with UniCell deconvolve," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    9. Xiaoyu Song & Jiayi Ji & Joseph H. Rothstein & Stacey E. Alexeeff & Lori C. Sakoda & Adriana Sistig & Ninah Achacoso & Eric Jorgenson & Alice S. Whittemore & Robert J. Klein & Laurel A. Habel & Pei Wa, 2023. "MiXcan: a framework for cell-type-aware transcriptome-wide association studies with an application to breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    10. Erick Armingol & Hratch M. Baghdassarian & Cameron Martino & Araceli Perez-Lopez & Caitlin Aamodt & Rob Knight & Nathan E. Lewis, 2022. "Context-aware deconvolution of cell–cell communication with Tensor-cell2cell," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    11. Fabian Peisker & Maurice Halder & James Nagai & Susanne Ziegler & Nadine Kaesler & Konrad Hoeft & Ronghui Li & Eric M. J. Bindels & Christoph Kuppe & Julia Moellmann & Michael Lehrke & Christian Stopp, 2022. "Mapping the cardiac vascular niche in heart failure," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    12. Sara M. Parigi & Ludvig Larsson & Srustidhar Das & Ricardo O. Ramirez Flores & Annika Frede & Kumar P. Tripathi & Oscar E. Diaz & Katja Selin & Rodrigo A. Morales & Xinxin Luo & Gustavo Monasterio & C, 2022. "The spatial transcriptomic landscape of the healing mouse intestine following damage," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    13. L. Mathur & B. Szalai & N. H. Du & R. Utharala & M. Ballinger & J. J. M. Landry & M. Ryckelynck & V. Benes & J. Saez-Rodriguez & C. A. Merten, 2022. "Combi-seq for multiplexed transcriptome-based profiling of drug combinations using deterministic barcoding in single-cell droplets," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Oliver J. Ziff & Jacob Neeves & Jamie Mitchell & Giulia Tyzack & Carlos Martinez-Ruiz & Raphaelle Luisier & Anob M. Chakrabarti & Nicholas McGranahan & Kevin Litchfield & Simon J. Boulton & Ammar Al-C, 2023. "Integrated transcriptome landscape of ALS identifies genome instability linked to TDP-43 pathology," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    15. Qilin Zhang & Ziyan Xu & Rui Han & Yunzhi Wang & Zhen Ye & Jiajun Zhu & Yixin Cai & Fan Zhang & Jiangyan Zhao & Boyuan Yao & Zhaoyu Qin & Nidan Qiao & Ruofan Huang & Jinwen Feng & Yongfei Wang & Wenti, 2024. "Proteogenomic characterization of skull-base chordoma," Nature Communications, Nature, vol. 15(1), pages 1-32, December.
    16. Kaja Kostyrko & Marta Román & Alex G. Lee & David R. Simpson & Phuong T. Dinh & Stanley G. Leung & Kieren D. Marini & Marcus R. Kelly & Joshua Broyde & Andrea Califano & Peter K. Jackson & E. Alejandr, 2023. "UHRF1 is a mediator of KRAS driven oncogenesis in lung adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    17. Chen Ni & Xiaohan Lou & Xiaohan Yao & Linlin Wang & Jiajia Wan & Xixi Duan & Jialu Liang & Kaili Zhang & Yuanyuan Yang & Li Zhang & Chanjun Sun & Zhenzhen Li & Ming Wang & Linyu Zhu & Dekang Lv & Zhih, 2022. "ZIP1+ fibroblasts protect lung cancer against chemotherapy via connexin-43 mediated intercellular Zn2+ transfer," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    18. Yoshiharu Muto & Eryn E. Dixon & Yasuhiro Yoshimura & Haojia Wu & Kohei Omachi & Nicolas Ledru & Parker C. Wilson & Andrew J. King & N. Eric Olson & Marvin G. Gunawan & Jay J. Kuo & Jennifer H. Cox & , 2022. "Defining cellular complexity in human autosomal dominant polycystic kidney disease by multimodal single cell analysis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    19. Andrew Gibson & Ramesh Ram & Rama Gangula & Yueran Li & Eric Mukherjee & Amy M. Palubinsky & Chelsea N. Campbell & Michael Thorne & Katherine C. Konvinse & Phuti Choshi & Pooja Deshpande & Sarah Pedre, 2024. "Multiomic single-cell sequencing defines tissue-specific responses in Stevens-Johnson syndrome and toxic epidermal necrolysis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    20. Ashley Byrne & Daniel Le & Kostianna Sereti & Hari Menon & Samir Vaidya & Neha Patel & Jessica Lund & Ana Xavier-Magalhães & Minyi Shi & Yuxin Liang & Timothy Sterne-Weiler & Zora Modrusan & William S, 2024. "Single-cell long-read targeted sequencing reveals transcriptional variation in ovarian cancer," Nature Communications, Nature, vol. 15(1), pages 1-13, 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:15:y:2024:i:1:d:10.1038_s41467-024-49595-1. 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.