IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-13471-0.html
   My bibliography  Save this article

Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4

Author

Listed:
  • Zhiyong Wang

    (University of California San Diego)

  • Victoria H. Wu

    (University of California San Diego
    University of California San Diego)

  • Michael M. Allevato

    (University of California San Diego
    University of California San Diego)

  • Mara Gilardi

    (University of California San Diego)

  • Yudou He

    (University of California San Diego)

  • Juan Luis Callejas-Valera

    (Sanford Research)

  • Lynn Vitale-Cross

    (National Institutes of Health)

  • Daniel Martin

    (National Institutes of Health)

  • Panomwat Amornphimoltham

    (Walailak University)

  • James Mcdermott

    (University of California San Diego)

  • Bryan S. Yung

    (University of California San Diego
    University of California San Diego)

  • Yusuke Goto

    (University of California San Diego)

  • Alfredo A. Molinolo

    (University of California San Diego)

  • Andrew B. Sharabi

    (University of California San Diego
    University of California San Diego)

  • Ezra E. W. Cohen

    (University of California San Diego
    University of California, San Diego)

  • Qianming Chen

    (Sichuan University)

  • J. Guy Lyons

    (University of Sydney
    Royal Prince Alfred Hospital
    Centenary Institute)

  • Ludmil B. Alexandrov

    (University of California San Diego
    University of California San Diego)

  • J. Silvio Gutkind

    (University of California San Diego
    University of California San Diego)

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Tobacco use is the main risk factor for HNSCC, and tobacco-associated HNSCCs have poor prognosis and response to available treatments. Recently approved anti-PD-1 immune checkpoint inhibitors showed limited activity (≤20%) in HNSCC, highlighting the need to identify new therapeutic options. For this, mouse models that accurately mimic the complexity of the HNSCC mutational landscape and tumor immune environment are urgently needed. Here, we report a mouse HNSCC model system that recapitulates the human tobacco-related HNSCC mutanome, in which tumors grow when implanted in the tongue of immunocompetent mice. These HNSCC lesions have similar immune infiltration and response rates to anti-PD-1 (≤20%) immunotherapy as human HNSCCs. Remarkably, we find that >70% of HNSCC lesions respond to intratumoral anti-CTLA-4. This syngeneic HNSCC mouse model provides a platform to accelerate the development of immunotherapeutic options for HNSCC.

Suggested Citation

  • Zhiyong Wang & Victoria H. Wu & Michael M. Allevato & Mara Gilardi & Yudou He & Juan Luis Callejas-Valera & Lynn Vitale-Cross & Daniel Martin & Panomwat Amornphimoltham & James Mcdermott & Bryan S. Yu, 2019. "Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13471-0
    DOI: 10.1038/s41467-019-13471-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-13471-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-13471-0?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
    ---><---

    Citations

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


    Cited by:

    1. Cong Fu & Robert Saddawi-Konefka & Jordan M. Chinai & Sarah Y. Kim & Ashwin V. Kammula & Jonathan J. Perera & Aiping Jiang & Payal Tiwari & Erin N. Kistler & Shiqi Tang & Sarah M. Luna & Kayla J. Colv, 2025. "In vivo CRISPR screening in head and neck cancer reveals Uchl5 as an immunotherapy target," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    2. Robert Saddawi-Konefka & Aoife O’Farrell & Farhoud Faraji & Lauren Clubb & Michael M. Allevato & Shawn M. Jensen & Bryan S. Yung & Zhiyong Wang & Victoria H. Wu & Nana-Ama Anang & Riyam Al Msari & Shi, 2022. "Lymphatic-preserving treatment sequencing with immune checkpoint inhibition unleashes cDC1-dependent antitumor immunity in HNSCC," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    3. Liang Zhang & Boxin Zhang & Meng-Jie Zhang & Wenlang Li & Hao Li & Yantian Jiao & Qi-Chao Yang & Shuo Wang & Yuan-Tong Liu & An Song & Hai-Tao Feng & Jianwei Sun & Ryan T. K. Kwok & Jacky W. Y. Lam & , 2025. "Trigger inducible tertiary lymphoid structure formation using covalent organic frameworks for cancer immunotherapy," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    4. Robert Saddawi-Konefka & Riyam Al Msari & Shiqi Tang & Chad Philips & Sayed Sadat & Lauren M. Clubb & Sarah Luna & Santiago Fassardi & Riley Jones & Ida Franiak Pietryga & Farhoud Faraji & Shiruyeh Sc, 2025. "The tumor-sentinel lymph node immuno-migratome reveals CCR7⁺ dendritic cells drive response to sequenced immunoradiotherapy," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    5. Binbin Wang & Robert Saddawi-Konefka & Lauren M. Clubb & Shiqi Tang & Di Wu & Sumit Mukherjee & Sahil Sahni & Saugato Rahman Dhruba & Xinping Yang & Sumeet Patiyal & Chi-Ping Day & Parth A. Desai & Cl, 2025. "Longitudinal liquid biopsy identifies an early predictive biomarker of immune checkpoint blockade response in head and neck squamous cell carcinoma," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    6. Dina V. Hingorani & Michael M. Allevato & Maria F. Camargo & Jacqueline Lesperance & Maryam A. Quraishi & Joseph Aguilera & Ida Franiak-Pietryga & Daniel J. Scanderbeg & Zhiyong Wang & Alfredo A. Moli, 2022. "Monomethyl auristatin antibody and peptide drug conjugates for trimodal cancer chemo-radio-immunotherapy," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    7. Caihua Zhang & Kang Li & Hongzhang Zhu & Maosheng Cheng & Shuang Chen & Rongsong Ling & Cheng Wang & Demeng Chen, 2024. "ITGB6 modulates resistance to anti-CD276 therapy in head and neck cancer by promoting PF4+ macrophage infiltration," Nature Communications, Nature, vol. 15(1), pages 1-23, 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:10:y:2019:i:1:d:10.1038_s41467-019-13471-0. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.