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

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

doi:10.1038/s41467-019-13471-0

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

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

Moores Cancer Center
University of California, San Diego
University of California
Sanford Research/USD
National Institute of Dental and Craniofacial Research (NIDCR)
Walailak University
Division of Infectious Diseases, Department of Medicine, University of California, San Diego
State Key Laboratory of Oral Disease
University of Sydney
Royal Prince Alfred Hospital
Centenary Institute of Cancer Medicine and Cell Biology

Research output: Contribution to journal › Article › peer-review

148 Citations (Scopus)

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.

Original language	English
Article number	5546
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13471-0
Publication status	Published - 1 Dec 2019
Externally published	Yes

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/s41467-019-13471-0

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Wang, Z., Wu, V. H., Allevato, M. M., Gilardi, M., He, Y., Luis Callejas-Valera, J., Vitale-Cross, L., Martin, D., Amornphimoltham, P., Mcdermott, J., Yung, B. S., Goto, Y., Molinolo, A. A., Sharabi, A. B., Cohen, E. E. W., Chen, Q., Lyons, J. G., Alexandrov, L. B., & Gutkind, J. S. (2019). Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4. Nature Communications, 10(1), Article 5546. https://doi.org/10.1038/s41467-019-13471-0

@article{ed992b11fc8d46e683222de5318c2f1a,

title = "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.",

author = "Zhiyong Wang and Wu, \{Victoria H.\} and Allevato, \{Michael M.\} and Mara Gilardi and Yudou He and \{Luis Callejas-Valera\}, Juan and Lynn Vitale-Cross and Daniel Martin and Panomwat Amornphimoltham and James Mcdermott and Yung, \{Bryan S.\} and Yusuke Goto and Molinolo, \{Alfredo A.\} and Sharabi, \{Andrew B.\} and Cohen, \{Ezra E.W.\} and Qianming Chen and Lyons, \{J. Guy\} and Alexandrov, \{Ludmil B.\} and Gutkind, \{J. Silvio\}",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-13471-0",

language = "English",

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Wang, Z, Wu, VH, Allevato, MM, Gilardi, M, He, Y, Luis Callejas-Valera, J, Vitale-Cross, L, Martin, D, Amornphimoltham, P, Mcdermott, J, Yung, BS, Goto, Y, Molinolo, AA, Sharabi, AB, Cohen, EEW, Chen, Q, Lyons, JG, Alexandrov, LB & Gutkind, JS 2019, 'Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4', Nature Communications, vol. 10, no. 1, 5546. https://doi.org/10.1038/s41467-019-13471-0

TY - JOUR

T1 - Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4

AU - Wang, Zhiyong

AU - Wu, Victoria H.

AU - Allevato, Michael M.

AU - Gilardi, Mara

AU - He, Yudou

AU - Luis Callejas-Valera, Juan

AU - Vitale-Cross, Lynn

AU - Martin, Daniel

AU - Amornphimoltham, Panomwat

AU - Mcdermott, James

AU - Yung, Bryan S.

AU - Goto, Yusuke

AU - Molinolo, Alfredo A.

AU - Sharabi, Andrew B.

AU - Cohen, Ezra E.W.

AU - Chen, Qianming

AU - Lyons, J. Guy

AU - Alexandrov, Ludmil B.

AU - Gutkind, J. Silvio

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85076027443

U2 - 10.1038/s41467-019-13471-0

DO - 10.1038/s41467-019-13471-0

M3 - Article

C2 - 31804466

AN - SCOPUS:85076027443

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5546

ER -

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

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