Genomics of NSCLC patients both affirm PD-L1 expression and predict their clinical responses to anti-PD-1 immunotherapy

BMC Cancer
Kim A BrogdenShireen Vali

Abstract

Programmed Death Ligand 1 (PD-L1) is a co-stimulatory and immune checkpoint protein. PD-L1 expression in non-small cell lung cancers (NSCLC) is a hallmark of adaptive resistance and its expression is often used to predict the outcome of Programmed Death 1 (PD-1) and PD-L1 immunotherapy treatments. However, clinical benefits do not occur in all patients and new approaches are needed to assist in selecting patients for PD-1 or PD-L1 immunotherapies. Here, we hypothesized that patient tumor cell genomics influenced cell signaling and expression of PD-L1, chemokines, and immunosuppressive molecules and these profiles could be used to predict patient clinical responses. We used a recent dataset from NSCLC patients treated with pembrolizumab. Deleterious gene mutational profiles in patient exomes were identified and annotated into a cancer network to create NSCLC patient-specific predictive computational simulation models. Validation checks were performed on the cancer network, simulation model predictions, and PD-1 match rates between patient-specific predicted and clinical responses. Expression profiles of these 24 chemokines and immunosuppressive molecules were used to identify patients who would or would not respond to PD-1 immun...Continue Reading

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Citations

Sep 5, 2019·Brain Sciences·Salvo Danilo LombardoAlessia Bramanti
Apr 8, 2020·Journal of Cardiovascular Translational Research·Sherry-Ann BrownJoerg Herrmann
Feb 15, 2020·Pathology, Research and Practice·Zhu LinglingZhou Qinghua

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Methods Mentioned

BETA
Assay
exome sequencing

Clinical Trials Mentioned

NCT01295827

Software Mentioned

FannsDB
Weka
PROVEAN
Polyphen
SIFT
Mutation Assessor
FATHMM

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