Cell genomics and immunosuppressive biomarker expression influence PD-L1 immunotherapy treatment responses in HNSCC-a computational study

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Aug;124(2):157-164. doi: 10.1016/j.oooo.2017.05.474. Epub 2017 May 25.

Abstract

Objectives: Programmed death-ligand 1 (PD-L1) expression is correlated with objective response rates to PD-1 and PD-L1 immunotherapies. However, both immunotherapies have only demonstrated 12%-24.8% objective response rates in patients with head and neck squamous cell carcinoma (HNSCC), demonstrating a need for a more accurate method to identify those who will respond before their therapy. Immunohistochemistry to detect PD-L1 reactivity in tumors can be challenging, and additional methods are needed to predict and confirm PD-L1 expression. Here, we hypothesized that HNSCC tumor cell genomics influences cell signaling and downstream effects on immunosuppressive biomarkers and that these profiles can predict patient clinical responses.

Study design: We identified deleterious gene mutations in SCC4, SCC15, and SCC25 and created cell line-specific predictive computational simulation models. The expression of 24 immunosuppressive biomarkers were then predicted and used to sort cell lines into those that would respond to PD-L1 immunotherapy and those that would not.

Results: SCC15 and SCC25 were identified as cell lines that would respond to PD-L1 immunotherapy treatment and SCC4 was identified as a cell line that would not likely respond to PD-L1 immunotherapy treatment.

Conclusions: This approach, when applied to HNSCC cells, has the ability to predict PD-L1 expression and predict PD-1- or PD-L1-targeted treatment responses in these patients.

MeSH terms

  • B7-H1 Antigen / genetics*
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / immunology*
  • Computational Biology
  • Gene Expression Regulation, Neoplastic
  • Genomics
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / immunology*
  • Humans
  • Immunohistochemistry
  • Immunotherapy
  • Mutation
  • Signal Transduction
  • Squamous Cell Carcinoma of Head and Neck
  • Translational Medical Research
  • Tumor Cells, Cultured

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human