Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4
| Autor: | Panomwat Amornphimoltham, Victoria Wu, J. Silvio Gutkind, James D. McDermott, J. Guy Lyons, Juan Luis Callejas-Valera, Bryan S. Yung, Michael M. Allevato, Ezra E.W. Cohen, Yusuke Goto, Lynn Vitale-Cross, Zhiyong Wang, Mara Gilardi, Yudou He, Andrew B. Sharabi, Daniel Martin, Qianming Chen, Ludmil B. Alexandrov, Alfredo A. Molinolo |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment General Physics and Astronomy Anti ctla 4 Mice Antineoplastic Agents Immunological 0302 clinical medicine Immune infiltration Medicine 2.1 Biological and endogenous factors Aetiology lcsh:Science Cancer Multidisciplinary Tumor Oral cancer 3. Good health Immunological Head and Neck Neoplasms 5.1 Pharmaceuticals 030220 oncology & carcinogenesis Carcinoma Squamous Cell Mouth Neoplasms Immunotherapy Development of treatments and therapeutic interventions Poor prognosis Science Immunology Antineoplastic Agents Article General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences Immune system Rare Diseases stomatognathic system Cell Line Tumor Tobacco Carcinoma otorhinolaryngologic diseases Animals Humans Dental/Oral and Craniofacial Disease neoplasms Tobacco Smoke and Health business.industry Animal General Chemistry medicine.disease Head and neck squamous-cell carcinoma Ipilimumab Disease Models Animal stomatognathic diseases 030104 developmental biology Good Health and Well Being Squamous Cell Disease Models Cancer research lcsh:Q business |
| Zdroj: | Nature communications, vol 10, iss 1 Nature Communications, Vol 10, Iss 1, Pp 1-13 (2019) Nature Communications |
| Popis: | 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. Tobacco use is one of the major risk factors for Head and neck squamous cell carcinoma (HNSCC). Here, the authors report an immune-competent syngeneic mouse model that mimics human tobacco-related HNSCC, and develops tumors in the tongue, and report a high response rate to anti-CTLA-4 therapy. |
| Databáze: | OpenAIRE |
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