Cancer immunogenomic approach to neoantigen discovery in a checkpoint blockade responsive murine model of oral cavity squamous cell carcinoma

Paul Zolkind, Dariusz Przybylski, Nemanja Marjanovic, Lan Nguyen, Tianxiang Lin, Tanner Johanns, Anton Alexandrov, Liye Zhou, Clint T. Allen, Alexander P. Miceli, Robert D. Schreiber, Maxim Artyomov, Gavin P. Dunn, Ravindra Uppaluri

Research output: Contribution to journalArticle

Abstract

Head and neck squamous cell carcinomas (HNSCC) are an ideal immunotherapy target due to their high mutation burden and frequent infiltration with lymphocytes. Preclinical models to investigate targeted and combination therapies as well as defining biomarkers to guide treatment represent an important need in the field. Immunogenomics approaches have illuminated the role of mutation-derived tumor neoantigens as potential biomarkers of response to checkpoint blockade as well as representing therapeutic vaccines. Here, we aimed to define a platform for checkpoint and other immunotherapy studies using syngeneic HNSCC cell line models (MOC2 and MOC22), and evaluated the association between mutation burden, predicted neoantigen landscape, infiltrating T cell populations and responsiveness of tumors to anti-PD1 therapy. We defined dramatic hematopoietic cell transcriptomic alterations in the MOC22 anti-PD1 responsive model in both tumor and draining lymph nodes. Using a cancer immunogenomics pipeline and validation with ELISPOT and tetramer analysis, we identified the H-2Kb-restricted ICAM1P315L (mICAM1) as a neoantigen in MOC22. Finally, we demonstrated that mICAM1 vaccination was able to protect against MOC22 tumor development defining mICAM1 as a bona fide neoantigen. Together these data define a pre-clinical HNSCC model system that provides a foundation for future investigations into combination and novel therapeutics.

Original languageEnglish (US)
Pages (from-to)4109-4119
Number of pages11
JournalOncotarget
Volume9
Issue number3
DOIs
StatePublished - 2018

Keywords

  • Head and neck cancer
  • Immunogenomics
  • Neoantigen

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Zolkind, P., Przybylski, D., Marjanovic, N., Nguyen, L., Lin, T., Johanns, T., Alexandrov, A., Zhou, L., Allen, C. T., Miceli, A. P., Schreiber, R. D., Artyomov, M., Dunn, G. P., & Uppaluri, R. (2018). Cancer immunogenomic approach to neoantigen discovery in a checkpoint blockade responsive murine model of oral cavity squamous cell carcinoma. Oncotarget, 9(3), 4109-4119. https://doi.org/10.18632/oncotarget.23751