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

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

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1038/s41467-019-13471-0
Journal or Publication Title: Nature Communications
Volume: 10
Number: 1
Date: 2019
Divisions: Immune Imaging
Depositing User: General Admin
Identification Number: 10.1038/s41467-019-13471-0
ISSN: 2041-1723
Date Deposited: 22 Dec 2020 02:54
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.

Creators:
Creators
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Wang, Zhiyong
UNSPECIFIED
Wu, Victoria H.
UNSPECIFIED
Allevato, Michael M.
UNSPECIFIED
Gilardi, Mara
UNSPECIFIED
He, Yudou
UNSPECIFIED
Luis Callejas-Valera, Juan
UNSPECIFIED
Vitale-Cross, Lynn
UNSPECIFIED
Martin, Daniel
UNSPECIFIED
Amornphimoltham, Panomwat
UNSPECIFIED
Mcdermott, James
UNSPECIFIED
Yung, Bryan S.
UNSPECIFIED
Goto, Yusuke
UNSPECIFIED
Molinolo, Alfredo A.
UNSPECIFIED
Sharabi, Andrew B.
UNSPECIFIED
Cohen, Ezra E. W.
UNSPECIFIED
Chen, Qianming
UNSPECIFIED
Lyons, J. Guy
UNSPECIFIED
Alexandrov, Ludmil B.
UNSPECIFIED
Gutkind, J. Silvio
UNSPECIFIED
Last Modified: 22 Dec 2020 02:54
URI: https://eprints.centenary.org.au/id/eprint/125

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