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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
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    Cited by:

    1. 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.
    2. 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.

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