Predicting PD-L1 expression on human cancer cells using next-generation sequencing information in computational simulation models.
Interaction of the programmed death-1 (PD-1) co-receptor on T cells with the programmed death-ligand 1 (PD-L1) on tumor cells can lead to immunosuppression, a key event in the pathogenesis of many tumors. Thus, determining the amount of PD-L1 in tumors by immunohistochemistry (IHC) is important as both a diagnostic aid and a clinical predictor of immunotherapy treatment success. Because IHC reactivity can vary, we developed computational simulation models to accurately predict PD-L1 expression as a complementary assay to affirm IHC reactivity.



Multiple myeloma (MM) and oral squamous cell carcinoma (SCC) cell lines were modeled as examples of our approach. Non-transformed cell models were first simulated to establish non-tumorigenic control baselines. Cell line genomic aberration profiles, from next-generation sequencing (NGS) information for MM.1S, U266B1, SCC4, SCC15, and SCC25 cell lines, were introduced into the workflow to create cancer cell line-specific simulation models. Percentage changes of PD-L1 expression with respect to control baselines were determined and verified against observed PD-L1 expression by ELISA, IHC, and flow cytometry on the same cells grown in culture.



The observed PD-L1 expression matched the predicted PD-L1 expression for MM.1S, U266B1, SCC4, SCC15, and SCC25 cell lines and clearly demonstrated that cell genomics play an integral role by influencing cell signaling and downstream effects on PD-L1 expression.



This concept can easily be extended to cancer patient cells where an accurate method to predict PD-L1 expression would affirm IHC results and improve its potential as a biomarker and a clinical predictor of treatment success.
Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA.
Emily A
EA
Lanzel
Iowa Institute for Oral Health Research, N423 DSB, College of Dentistry, The University of Iowa, 801 Newton Road, Iowa City, IA, 52242, USA.
M
M
Paula Gomez Hernandez
Iowa Institute for Oral Health Research, N423 DSB, College of Dentistry, The University of Iowa, 801 Newton Road, Iowa City, IA, 52242, USA.
Amber M
AM
Bates
Iowa Institute for Oral Health Research, N423 DSB, College of Dentistry, The University of Iowa, 801 Newton Road, Iowa City, IA, 52242, USA.
Christopher N
CN
Treinen
Iowa Institute for Oral Health Research, N423 DSB, College of Dentistry, The University of Iowa, 801 Newton Road, Iowa City, IA, 52242, USA.
Emily E
EE
Starman
Iowa Institute for Oral Health Research, N423 DSB, College of Dentistry, The University of Iowa, 801 Newton Road, Iowa City, IA, 52242, USA.
Carol L
CL
Fischer
Cellworks Research India Ltd, Whitefield, Bangalore, India.
Deepak
D
Parashar
College of Dentistry, University of Nebraska Medical Center, 40th and Holdrege, Lincoln, NE, USA.
Janet M
JM
Guthmiller
Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, IA, USA.
Georgia K
GK
Johnson
Cellworks Research India Ltd, Whitefield, Bangalore, India.|Cellworks Group Inc, 2033 Gateway Place Suite 500, San Jose, CA, USA.
Taher
T
Abbasi
Cellworks Research India Ltd, Whitefield, Bangalore, India.|Cellworks Group Inc, 2033 Gateway Place Suite 500, San Jose, CA, USA.
Shireen
S
Vali
Iowa Institute for Oral Health Research, N423 DSB, College of Dentistry, The University of Iowa, 801 Newton Road, Iowa City, IA, 52242, USA. kim-brogden@uiowa.edu.|Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, IA, USA. kim-brogden@uiowa.edu.
Kim A
KA
Brogden
D000328:Adult; D060890:B7-H1 Antigen / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D003198:Computer Simulation; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology
D060890:B7-H1 Antigen; C423236:CD274 protein, human
Computational modeling; Multiple myeloma; Oral squamous cell carcinoma; PD-L1; Simulation modeling
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