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.

Details

Title
Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4
Author
Wang, Zhiyong 1   VIAFID ORCID Logo  ; Wu, Victoria H 2 ; Allevato, Michael M 2 ; Gilardi, Mara 1 ; He, Yudou 3   VIAFID ORCID Logo  ; Callejas-Valera, Juan Luis 4   VIAFID ORCID Logo  ; Vitale-Cross, Lynn 5 ; Martin, Daniel 5 ; Amornphimoltham, Panomwat 6 ; Mcdermott, James 1 ; Yung, Bryan S 2 ; Goto, Yusuke 1 ; Molinolo, Alfredo A 1 ; Sharabi, Andrew B 7 ; Cohen, Ezra E W 8 ; Chen, Qianming 9 ; J Guy Lyons 10   VIAFID ORCID Logo  ; Alexandrov, Ludmil B 11   VIAFID ORCID Logo  ; J Silvio Gutkind 2   VIAFID ORCID Logo 

 Moores Cancer Center, University of California San Diego, La Jolla, CA, USA 
 Moores Cancer Center, University of California San Diego, La Jolla, CA, USA; Department of Pharmacology, University of California San Diego, La Jolla, CA, USA 
 Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA 
 Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA 
 National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA 
 International College of Dentistry, Walailak University, Nakhon Si Thammarat, Thailand 
 Moores Cancer Center, University of California San Diego, La Jolla, CA, USA; Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA 
 Moores Cancer Center, University of California San Diego, La Jolla, CA, USA; Department of Medicine, Division of Hematology-Oncology, University of California, San Diego, La Jolla, CA, USA 
 State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China 
10  Dermatology, Bosch Institute, University of Sydney, Camperdown, NSW, Australia; Cancer Services, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Centenary Institute, Camperdown, NSW, Australia 
11  Moores Cancer Center, University of California San Diego, La Jolla, CA, USA; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA 
Pages
1-13
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2322133469
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.