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

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. Yung, Yusuke Goto, Alfredo A. Molinolo, Andrew B. Sharabi, Ezra E. W. Cohen, Qianming Chen, J. Guy Lyons, Ludmil B. Alexandrov and J. Silvio Gutkind ()
Additional contact information
Zhiyong Wang: University of California San Diego
Victoria H. Wu: University of California San Diego
Michael M. Allevato: 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
Yusuke Goto: University of California San Diego
Alfredo A. Molinolo: University of California San Diego
Andrew B. Sharabi: University of California San Diego
Ezra E. W. Cohen: University of California San Diego
Qianming Chen: Sichuan University
J. Guy Lyons: University of Sydney
Ludmil B. Alexandrov: University of California San Diego
J. Silvio Gutkind: University of California San Diego

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13471-0

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