Evidence map›Paper›PMID 27688163›Full record

ArticleCancer immunology, immunotherapy : CII2016

Predicting PD-L1 expression on human cancer cells using next-generation sequencing information in computational simulation models.

Emily A Lanzel, M Paula Gomez Hernandez, Amber M Bates, Christopher N Treinen, Emily E Starman, Carol L Fischer, Deepak Parashar, Janet M Guthmiller, Georgia K Johnson, Taher Abbasi and 2 more

Open access · greenAbstract read
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

Emily A LanzelDepartment of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA.
M Paula Gomez HernandezIowa Institute for Oral Health Research, N423 DSB, College of Dentistry, The University of Iowa, 801 Newton Road, Iowa City, IA, 52242, USA.
Amber M BatesIowa Institute for Oral Health Research, N423 DSB, College of Dentistry, The University of Iowa, 801 Newton Road, Iowa City, IA, 52242, USA.
Christopher N TreinenIowa Institute for Oral Health Research, N423 DSB, College of Dentistry, The University of Iowa, 801 Newton Road, Iowa City, IA, 52242, USA.
Emily E StarmanIowa Institute for Oral Health Research, N423 DSB, College of Dentistry, The University of Iowa, 801 Newton Road, Iowa City, IA, 52242, USA.
Carol L FischerIowa Institute for Oral Health Research, N423 DSB, College of Dentistry, The University of Iowa, 801 Newton Road, Iowa City, IA, 52242, USA.
Deepak ParasharCellworks Research India Ltd, Whitefield, Bangalore, India.
Janet M GuthmillerCollege of Dentistry, University of Nebraska Medical Center, 40th and Holdrege, Lincoln, NE, USA.
Georgia K JohnsonDepartment of Periodontics, College of Dentistry, The University of Iowa, Iowa City, IA, USA.
Taher AbbasiCellworks Research India Ltd, Whitefield, Bangalore, India.
Shireen ValiCellworks Research India Ltd, Whitefield, Bangalore, India.
Kim A BrogdenIowa 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.
University of Iowa · USCellworks Research (India) · INUniversity of Nebraska Medical Center · US

Funding

University of Iowa Institutional Training Program in Oral Health ResearchT90DE023520 · NIDCR · UNIVERSITY OF IOWA · PI STEVEN M. LEVY · 2013 to 2026
$5.6M
Defensin-induced Adaptive Immunity to HagBR01DE014390 · NIDCR · UNIVERSITY OF IOWA · PI BROGDEN, KIM A · 2003 to 2014
$3.4M
NIDCR NIH HHS R01 DE014390NIDCR NIH HHS T90 DE023520
6 · The paper itself

Abstract

purposeInteraction 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.

methodsMultiple 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.

resultThe 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.

conclusionThis 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.

Indexed as

AdultB7-H1 AntigenCarcinoma, Squamous CellComputer SimulationHumansMiddle AgedModels, BiologicalMolecular Dynamics SimulationMouth NeoplasmsMultiple MyelomaB7-H1 AntigenCD274 protein, humanComputational modelingMultiple myelomaOral squamous cell carcinomaPD-L1Simulation modeling

Identifiers

PMID27688163
PMCPMC5394567
OpenAlexW2525896884

What OpenQuestion holds

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LicenceTDM
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.