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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.
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1 Moores Cancer Center, University of California San Diego, La Jolla, CA, USA
2 Moores Cancer Center, University of California San Diego, La Jolla, CA, USA; Department of Pharmacology, University of California San Diego, La Jolla, CA, USA
3 Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA
4 Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA
5 National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA
6 International College of Dentistry, Walailak University, Nakhon Si Thammarat, Thailand
7 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
8 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
9 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