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

Publication date: Available online 25 May 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Amber M. Bates, Emily Lanzel, Fang Qian, Taher Abbasi, Shireen Vali, Kim A. Brogden
ObjectivesPD-L1 expression is correlated with objective responses rates (ORR) to PD-1 and PD-L1 immunotherapies. However, both immunotherapies have only demonstrated 12.0-24.8% ORR in patients with HNSCC showing a need for a more accurate method to identify those who will respond prior to 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 DesignWe 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 or would not respond to PD-L1 immunotherapy.ResultsSCC15 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.ConclusionsThis approach, when applied to patient HNSCC cancer cells, has the ability to predict PD-L1 expression and predict PD-1 or PD-L1 targeted treatment responses in those patients.



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