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

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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

Authors: Bates AM, Lanzel EA, Qian F, Abbasi T, Vali S, Brogden KA

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.

PMID: 28756882 [PubMed - in process]

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