IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-58436-8.html
   My bibliography  Save this article

Angiogenic and immune predictors of neoadjuvant axitinib response in renal cell carcinoma with venous tumour thrombus

Author

Listed:
  • Rebecca Wray

    (University of Cambridge
    University of Cambridge
    University of Cambridge)

  • Hania Paverd

    (University of Cambridge
    University of Cambridge
    University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust)

  • Ines Machado

    (University of Cambridge
    University of Cambridge)

  • Johanna Barbieri

    (University of Cambridge)

  • Farhana Easita

    (University of Cambridge)

  • Abigail R. Edwards

    (University of Cambridge)

  • Ferdia A. Gallagher

    (Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

  • Iosif A. Mendichovszky

    (Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

  • Thomas J. Mitchell

    (University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

  • Maike Roche

    (University of Cambridge)

  • Jacqueline D. Shields

    (University of Nottingham Biodiscovery Institute)

  • Stephan Ursprung

    (Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

  • Lauren Wallis

    (University of Warwick)

  • Anne Y. Warren

    (Cambridge University Hospitals NHS Foundation Trust)

  • Sarah J. Welsh

    (Royal Devon University Healthcare NHS Foundation Trust)

  • Mireia Crispin-Ortuzar

    (University of Cambridge
    University of Cambridge
    University of Cambridge)

  • Grant D. Stewart

    (University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

  • James O. Jones

    (University of Cambridge
    University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

Abstract

Venous tumour thrombus (VTT), where the primary tumour invades the renal vein and inferior vena cava, affects 10–15% of renal cell carcinoma (RCC) patients. Curative surgery for VTT is high-risk, but neoadjuvant therapy may improve outcomes. The NAXIVA trial demonstrated a 35% VTT response rate after 8 weeks of neoadjuvant axitinib, a VEGFR-directed therapy. However, understanding non-response is critical for better treatment. Here we show that response to axitinib in this setting is characterised by a distinct and predictable set of features. We conduct a multiparametric investigation of samples collected during NAXIVA using digital pathology, flow cytometry, plasma cytokine profiling and RNA sequencing. Responders have higher baseline microvessel density and increased induction of VEGF-A and PlGF during treatment. A multi-modal machine learning model integrating features predict response with an AUC of 0.868, improving to 0.945 when using features from week 3. Key predictive features include plasma CCL17 and IL-12. These findings may guide future treatment strategies for VTT, improving the clinical management of this challenging scenario.

Suggested Citation

  • Rebecca Wray & Hania Paverd & Ines Machado & Johanna Barbieri & Farhana Easita & Abigail R. Edwards & Ferdia A. Gallagher & Iosif A. Mendichovszky & Thomas J. Mitchell & Maike Roche & Jacqueline D. Sh, 2025. "Angiogenic and immune predictors of neoadjuvant axitinib response in renal cell carcinoma with venous tumour thrombus," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58436-8
    DOI: 10.1038/s41467-025-58436-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-58436-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-025-58436-8?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. Stephen-John Sammut & Mireia Crispin-Ortuzar & Suet-Feung Chin & Elena Provenzano & Helen A. Bardwell & Wenxin Ma & Wei Cope & Ali Dariush & Sarah-Jane Dawson & Jean E. Abraham & Janet Dunn & Louise H, 2022. "Multi-omic machine learning predictor of breast cancer therapy response," Nature, Nature, vol. 601(7894), pages 623-629, January.
    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. James M. Dolezal & Andrew Srisuwananukorn & Dmitry Karpeyev & Siddhi Ramesh & Sara Kochanny & Brittany Cody & Aaron S. Mansfield & Sagar Rakshit & Radhika Bansal & Melanie C. Bois & Aaron O. Bungum & , 2022. "Uncertainty-informed deep learning models enable high-confidence predictions for digital histopathology," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Mattia Rediti & Aranzazu Fernandez-Martinez & David Venet & Françoise Rothé & Katherine A. Hoadley & Joel S. Parker & Baljit Singh & Jordan D. Campbell & Karla V. Ballman & David W. Hillman & Eric P. , 2023. "Immunological and clinicopathological features predict HER2-positive breast cancer prognosis in the neoadjuvant NeoALTTO and CALGB 40601 randomized trials," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Umberto Perron & Elena Grassi & Aikaterini Chatzipli & Marco Viviani & Emre Karakoc & Lucia Trastulla & Lorenzo M. Brochier & Claudio Isella & Eugenia R. Zanella & Hagen Klett & Ivan Molineris & Julia, 2024. "Integrative ensemble modelling of cetuximab sensitivity in colorectal cancer patient-derived xenografts," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    4. Kevin M. Boehm & Omar S. M. El Nahhas & Antonio Marra & Michele Waters & Justin Jee & Lior Braunstein & Nikolaus Schultz & Pier Selenica & Hannah Y. Wen & Britta Weigelt & Evan D. Paul & Pavol Cekan &, 2025. "Multimodal histopathologic models stratify hormone receptor-positive early breast cancer," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    5. 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.
    6. Yuan Gao & Sofia Ventura-Diaz & Xin Wang & Muzhen He & Zeyan Xu & Arlene Weir & Hong-Yu Zhou & Tianyu Zhang & Frederieke H. Duijnhoven & Luyi Han & Xiaomei Li & Anna D’Angelo & Valentina Longo & Zaiyi, 2024. "An explainable longitudinal multi-modal fusion model for predicting neoadjuvant therapy response in women with breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    7. Joyce V. Lee & Filomena Housley & Christina Yau & Rachel Nakagawa & Juliane Winkler & Johanna M. Anttila & Pauliina M. Munne & Mariel Savelius & Kathleen E. Houlahan & Daniel Mark & Golzar Hemmati & G, 2022. "Combinatorial immunotherapies overcome MYC-driven immune evasion in triple negative breast cancer," Nature Communications, Nature, vol. 13(1), pages 1-12, 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:16:y:2025:i:1:d:10.1038_s41467-025-58436-8. 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.