机构：[1]Moores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, USA.[2]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]Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA.[8]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 2050, Australia.[11]Cancer Services, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.[12]Centenary Institute, Camperdown, NSW 2050, Australia.
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.
基金：
National Institute of Dental and Craniofacial
Research (NIH/NIDCR, R01DE026644, R01DE026870, and U01DE028227), National
Natural Science Foundation of China (81602376, 81520108009, and 81621062), and 111
Project of MOE (B14038), China. Mara Gilardi was supported by FIRC-AIRC fellowship
for abroad (Italian Foundation for cancer research). M.M.A. was supported by the
Pharmacological Sciences Training Program (5T32GM007752-39 and 5T32GM007752-
40).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
最新[2023]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
第一作者：
第一作者机构：[1]Moores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, USA.
共同第一作者：
通讯作者：
通讯机构：[1]Moores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, USA.[2]Department of Pharmacology, University of California San Diego, La Jolla, CA, USA.
推荐引用方式(GB/T 7714)：
Wang Zhiyong,Wu Victoria H,Allevato Michael M,et al.Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4.[J].Nature communications.2019,10(1):5546.doi:10.1038/s41467-019-13471-0.
APA：
Wang Zhiyong,Wu Victoria H,Allevato Michael M,Gilardi Mara,He Yudou...&Gutkind J Silvio.(2019).Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4..Nature communications,10,(1)
MLA：
Wang Zhiyong,et al."Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4.".Nature communications 10..1(2019):5546
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