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

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.

• Authors: 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, J Silvio Gutkind
• Journal: Nature communications (Nat Commun) Vol. 10 Issue 1 Pg. 5546 (12 05 2019) ISSN: 2041-1723 [Electronic] England
• PMID: 31804466 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Immunological
• Ipilimumab

Topics

• Animals
• Antineoplastic Agents, Immunological (therapeutic use)
• Carcinoma, Squamous Cell (chemically induced, therapy)
• Cell Line, Tumor
• Disease Models, Animal
• Head and Neck Neoplasms (chemically induced, therapy)
• Humans
• Immunotherapy (methods)
• Ipilimumab (therapeutic use)
• Mice
• Mouth Neoplasms (chemically induced, therapy)
• Nicotiana (adverse effects)