IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43290-3.html
   My bibliography  Save this article

Delineating the interplay between oncogenic pathways and immunity in anaplastic Wilms tumors

Author

Listed:
  • Xiaoping Su

    (The University of Texas MD Anderson Cancer Center)

  • Xiaofan Lu

    (Department of Cancer and Functional Genomics, Institute of Genetics and Molecular and Cellular Biology, CNRS/INSERM/UNISTRA
    China Pharmaceutical University)

  • Sehrish Khan Bazai

    (Department of Cancer and Functional Genomics, Institute of Genetics and Molecular and Cellular Biology, CNRS/INSERM/UNISTRA)

  • Linda Dainese

    (Sorbonne Université
    Sorbonne Université
    Sorbonne Université)

  • Arnauld Verschuur

    (Hôpital d’Enfants de La Timone)

  • Benoit Dumont

    (Centre Léon Bérard, Institut d’Hématologie et d’Oncologie Pédiatrique (IHOPe))

  • Roger Mouawad

    (Assistance-Publique Hôpitaux de Paris)

  • Li Xu

    (China Pharmaceutical University)

  • Wenxuan Cheng

    (China Pharmaceutical University)

  • Fangrong Yan

    (China Pharmaceutical University)

  • Sabine Irtan

    (Sorbonne Université)

  • Véronique Lindner

    (CHRU Strasbourg)

  • Catherine Paillard

    (Strasbourg Université)

  • Yves Bouc

    (Sorbonne Université)

  • Aurore Coulomb

    (Sorbonne Université
    Sorbonne Université
    Sorbonne Université)

  • Gabriel G. Malouf

    (Department of Cancer and Functional Genomics, Institute of Genetics and Molecular and Cellular Biology, CNRS/INSERM/UNISTRA
    Strasbourg University)

Abstract

Wilms tumors are highly curable in up to 90% of cases with a combination of surgery and radio-chemotherapy, but treatment-resistant types such as diffuse anaplastic Wilms tumors pose significant therapeutic challenges. Our multi-omics profiling unveils a distinct desert-like diffuse anaplastic Wilms tumor subtype marked by immune/stromal cell depletion, TP53 alterations, and cGAS-STING pathway downregulation, accounting for one-third of all diffuse anaplastic cases. This subtype, also characterized by reduced CD8 and CD3 infiltration and active oncogenic pathways involving histone deacetylase and DNA repair, correlates with poor clinical outcomes. These oncogenic pathways are found to be conserved in anaplastic Wilms tumor cell models. We identify histone deacetylase and/or WEE1 inhibitors as potential therapeutic vulnerabilities in these tumors, which might also restore tumor immunogenicity and potentially enhance the effects of immunotherapy. These insights offer a foundation for predicting outcomes and personalizing treatment strategies for aggressive pediatric Wilms tumors, tailored to individual immunological landscapes.

Suggested Citation

  • Xiaoping Su & Xiaofan Lu & Sehrish Khan Bazai & Linda Dainese & Arnauld Verschuur & Benoit Dumont & Roger Mouawad & Li Xu & Wenxuan Cheng & Fangrong Yan & Sabine Irtan & Véronique Lindner & Catherine , 2023. "Delineating the interplay between oncogenic pathways and immunity in anaplastic Wilms tumors," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43290-3
    DOI: 10.1038/s41467-023-43290-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43290-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43290-3?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. David A. Barbie & Pablo Tamayo & Jesse S. Boehm & So Young Kim & Susan E. Moody & Ian F. Dunn & Anna C. Schinzel & Peter Sandy & Etienne Meylan & Claudia Scholl & Stefan Fröhling & Edmond M. Chan & Ma, 2009. "Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1," Nature, Nature, vol. 462(7269), pages 108-112, November.
    2. Kosuke Yoshihara & Maria Shahmoradgoli & Emmanuel Martínez & Rahulsimham Vegesna & Hoon Kim & Wandaliz Torres-Garcia & Victor Treviño & Hui Shen & Peter W. Laird & Douglas A. Levine & Scott L. Carter , 2013. "Inferring tumour purity and stromal and immune cell admixture from expression data," Nature Communications, Nature, vol. 4(1), pages 1-11, December.
    3. Yujin Hoshida & Jean-Philippe Brunet & Pablo Tamayo & Todd R Golub & Jill P Mesirov, 2007. "Subclass Mapping: Identifying Common Subtypes in Independent Disease Data Sets," PLOS ONE, Public Library of Science, vol. 2(11), pages 1-8, November.
    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. Wanzun Lin & Li Chen & Haojiong Zhang & Xianxin Qiu & Qingting Huang & Fangzhu Wan & Ziyu Le & Shikai Geng & Anlan Zhang & Sufang Qiu & Long Chen & Lin Kong & Jiade J. Lu, 2023. "Tumor-intrinsic YTHDF1 drives immune evasion and resistance to immune checkpoint inhibitors via promoting MHC-I degradation," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    2. Yuanyuan Qu & Xiaohui Wu & Aihetaimujiang Anwaier & Jinwen Feng & Wenhao Xu & Xiaoru Pei & Yu Zhu & Yang Liu & Lin Bai & Guojian Yang & Xi Tian & Jiaqi Su & Guo-Hai Shi & Da-Long Cao & Fujiang Xu & Yu, 2022. "Proteogenomic characterization of MiT family translocation renal cell carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Yin Li & Manling Jiang & Ling Aye & Li Luo & Yong Zhang & Fengkai Xu & Yongqi Wei & Dan Peng & Xiang He & Jie Gu & Xiaofang Yu & Guoping Li & Di Ge & Chunlai Lu, 2024. "UPP1 promotes lung adenocarcinoma progression through the induction of an immunosuppressive microenvironment," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    4. Brian D. Lehmann & Antonio Colaprico & Tiago C. Silva & Jianjiao Chen & Hanbing An & Yuguang Ban & Hanchen Huang & Lily Wang & Jamaal L. James & Justin M. Balko & Paula I. Gonzalez-Ericsson & Melinda , 2021. "Multi-omics analysis identifies therapeutic vulnerabilities in triple-negative breast cancer subtypes," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    5. Zhenmei Yao & Ning Xu & Guoguo Shang & Haixing Wang & Hui Tao & Yunzhi Wang & Zhaoyu Qin & Subei Tan & Jinwen Feng & Jiajun Zhu & Fahan Ma & Sha Tian & Qiao Zhang & Yuanyuan Qu & Jun Hou & Jianming Gu, 2023. "Proteogenomics of different urothelial bladder cancer stages reveals distinct molecular features for papillary cancer and carcinoma in situ," Nature Communications, Nature, vol. 14(1), pages 1-25, 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. Hailiang Zhang & Lin Bai & Xin-Qiang Wu & Xi Tian & Jinwen Feng & Xiaohui Wu & Guo-Hai Shi & Xiaoru Pei & Jiacheng Lyu & Guojian Yang & Yang Liu & Wenhao Xu & Aihetaimujiang Anwaier & Yu Zhu & Da-Long, 2023. "Proteogenomics of clear cell renal cell carcinoma response to tyrosine kinase inhibitor," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    8. Yuanyuan Qu & Jinwen Feng & Xiaohui Wu & Lin Bai & Wenhao Xu & Lingli Zhu & Yang Liu & Fujiang Xu & Xuan Zhang & Guojian Yang & Jiacheng Lv & Xiuping Chen & Guo-Hai Shi & Hong-Kai Wang & Da-Long Cao &, 2022. "A proteogenomic analysis of clear cell renal cell carcinoma in a Chinese population," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    9. Shaoshuai Tang & Yunzhi Wang & Rongkui Luo & Rundong Fang & Yufeng Liu & Hang Xiang & Peng Ran & Yexin Tong & Mingjun Sun & Subei Tan & Wen Huang & Jie Huang & Jiacheng Lv & Ning Xu & Zhenmei Yao & Qi, 2024. "Proteomic characterization identifies clinically relevant subgroups of soft tissue sarcoma," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    10. Qingnan Liang & Yuefan Huang & Shan He & Ken Chen, 2023. "Pathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Miles C. Andrews & Junna Oba & Chang-Jiun Wu & Haifeng Zhu & Tatiana Karpinets & Caitlin A. Creasy & Marie-Andrée Forget & Xiaoxing Yu & Xingzhi Song & Xizeng Mao & A. Gordon Robertson & Gabriele Roma, 2022. "Multi-modal molecular programs regulate melanoma cell state," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    12. Lucia Taraborrelli & Yasin Şenbabaoğlu & Lifen Wang & Junghyun Lim & Kerrigan Blake & Noelyn Kljavin & Sarah Gierke & Alexis Scherl & James Ziai & Erin McNamara & Mark Owyong & Shilpa Rao & Aslihan Ka, 2023. "Tumor-intrinsic expression of the autophagy gene Atg16l1 suppresses anti-tumor immunity in colorectal cancer," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    13. Jennifer G. Abelin & Erik J. Bergstrom & Keith D. Rivera & Hannah B. Taylor & Susan Klaeger & Charles Xu & Eva K. Verzani & C. Jackson White & Hilina B. Woldemichael & Maya Virshup & Meagan E. Olive &, 2023. "Workflow enabling deepscale immunopeptidome, proteome, ubiquitylome, phosphoproteome, and acetylome analyses of sample-limited tissues," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    14. Su Yin Lim & Elena Shklovskaya & Jenny H. Lee & Bernadette Pedersen & Ashleigh Stewart & Zizhen Ming & Mal Irvine & Brindha Shivalingam & Robyn P. M. Saw & Alexander M. Menzies & Matteo S. Carlino & R, 2023. "The molecular and functional landscape of resistance to immune checkpoint blockade in melanoma," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    15. Xiaodong Liu & Ke Zhang & Neslihan A. Kaya & Zhe Jia & Dafei Wu & Tingting Chen & Zhiyuan Liu & Sinan Zhu & Axel M. Hillmer & Torsten Wuestefeld & Jin Liu & Yun Shen Chan & Zheng Hu & Liang Ma & Li Ji, 2024. "Tumor phylogeography reveals block-shaped spatial heterogeneity and the mode of evolution in Hepatocellular Carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    16. Zheqi Li & Olivia McGinn & Yang Wu & Amir Bahreini & Nolan M. Priedigkeit & Kai Ding & Sayali Onkar & Caleb Lampenfeld & Carol A. Sartorius & Lori Miller & Margaret Rosenzweig & Ofir Cohen & Nikhil Wa, 2022. "ESR1 mutant breast cancers show elevated basal cytokeratins and immune activation," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    17. Christel F. A. Ramirez & Daniel Taranto & Masami Ando-Kuri & Marnix H. P. Groot & Efi Tsouri & Zhijie Huang & Daniel Groot & Roelof J. C. Kluin & Daan J. Kloosterman & Joanne Verheij & Jing Xu & Seren, 2024. "Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    18. Shixiang Wang & Chen-Yi Wu & Ming-Ming He & Jia-Xin Yong & Yan-Xing Chen & Li-Mei Qian & Jin-Ling Zhang & Zhao-Lei Zeng & Rui-Hua Xu & Feng Wang & Qi Zhao, 2024. "Machine learning-based extrachromosomal DNA identification in large-scale cohorts reveals its clinical implications in cancer," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    19. Julia Joung & Paul C. Kirchgatterer & Ankita Singh & Jang H. Cho & Suchita P. Nety & Rebecca C. Larson & Rhiannon K. Macrae & Rebecca Deasy & Yuen-Yi Tseng & Marcela V. Maus & Feng Zhang, 2022. "CRISPR activation screen identifies BCL-2 proteins and B3GNT2 as drivers of cancer resistance to T cell-mediated cytotoxicity," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    20. María-Jesús Lobón-Iglesias & Mamy Andrianteranagna & Zhi-Yan Han & Céline Chauvin & Julien Masliah-Planchon & Valeria Manriquez & Arnault Tauziede-Espariat & Sandrina Turczynski & Rachida Bouarich-Bou, 2023. "Imaging and multi-omics datasets converge to define different neural progenitor origins for ATRT-SHH subgroups," Nature Communications, Nature, vol. 14(1), pages 1-21, 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:14:y:2023:i:1:d:10.1038_s41467-023-43290-3. 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.