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

Amber M Bates; Emily A Lanzel; Fang Qian; Taher Abbasi; Shireen Vali; Kim A Brogden

doi:10.1016/j.oooo.2017.05.474

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

Journal article

Open access

Peer reviewed

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

Amber M Bates, Emily A Lanzel, Fang Qian, Taher Abbasi, Shireen Vali and Kim A Brogden

Oral surgery, oral medicine, oral pathology and oral radiology, Vol.124(2), pp.157-164

08/2017

DOI: 10.1016/j.oooo.2017.05.474

PMCID: PMC5539917

PMID: 28756882

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Abstract

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. 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. 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. 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.

Immunohistochemistry

Signal Transduction

Carcinoma, Squamous Cell - genetics

Genomics

Humans

Translational Medical Research

Computational Biology

Gene Expression Regulation, Neoplastic

B7-H1 Antigen - genetics

Carcinoma, Squamous Cell - immunology

Head and Neck Neoplasms - immunology

Squamous Cell Carcinoma of Head and Neck

Immunotherapy

Head and Neck Neoplasms - genetics

Biomarkers, Tumor - genetics

Mutation

Tumor Cells, Cultured

Details

Title: Subtitle: Cell genomics and immunosuppressive biomarker expression influence PD-L1 immunotherapy treatment responses in HNSCC-a computational study
Creators: Amber M Bates - Iowa Institute for Oral Health Research, College of Dentistry, University of Iowa, Iowa City, IA, USA
Emily A Lanzel - Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA
Fang Qian - Iowa Institute for Oral Health Research, College of Dentistry, University of Iowa, Iowa City, IA, USA; Division of Biostatistics and Research Design, College of Dentistry, University of Iowa, Iowa City, IA, USA
Taher Abbasi - Cellworks Group, Inc., San Jose, CA, USA
Shireen Vali - Cellworks Group, Inc., San Jose, CA, USA
Kim A Brogden - Iowa Institute for Oral Health Research, College of Dentistry, University of Iowa, Iowa City, IA, USA. Electronic address: Kim-brogden@uiowa.edu
Resource Type: Journal article
Publication Details: Oral surgery, oral medicine, oral pathology and oral radiology, Vol.124(2), pp.157-164
DOI: 10.1016/j.oooo.2017.05.474
PMID: 28756882
PMCID: PMC5539917
NLM abbreviation: Oral Surg Oral Med Oral Pathol Oral Radiol
ISSN: 2212-4403
eISSN: 2212-4411
Publisher: United States
Grant note: R01 DE014390 / NIDCR NIH HHS T90 DE023520 / NIDCR NIH HHS
Language: English
Date published: 08/2017
Academic Unit: Preventive and Community Dentistry; Oral Pathology, Radiology and Medicine; Dental Research; Periodontics
Record Identifier: 9984065804502771

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