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

Nat Commun. 2019 Dec 5;10(1):5546. doi: 10.1038/s41467-019-13471-0.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antineoplastic Agents, Immunological
  • Ipilimumab