TY - JOUR
T1 - Prediction of PD‐l1 expression in neuroblastoma via computational modeling
AU - Lombardo, Salvo Danilo
AU - Presti, Mario
AU - Mangano, Katia
AU - Petralia, Maria Cristina
AU - Basile, Maria Sofia
AU - Libra, Massimo
AU - Candido, Saverio
AU - Fagone, Paolo
AU - Mazzon, Emanuela
AU - Nicoletti, Ferdinando
AU - Bramanti, Alessia
PY - 2019/9
Y1 - 2019/9
N2 - Immunotherapy is a promising new therapeutic approach for neuroblastoma (NBM): An anti-GD2 vaccine combined with orally administered soluble beta-glucan is undergoing a phase II clinical trial and nivolumab and ipilimumab are being tested in recurrent and refractory tumors. Unfortunately, predictive biomarkers of response to immunotherapy are currently not available for NBM patients. The aim of this study was to create a computational network model simulating the different intracellular pathways involved in NBM, in order to predict how the tumor phenotype may be influenced to increase the sensitivity to anti-programmed cell death-ligand-1 (PD-L1)/programmed cell death-1 (PD-1) immunotherapy. The model runs on COPASI software. In order to determine the influence of intracellular signaling pathways on the expression of PD-L1 in NBM, we first developed an integrated network of protein kinase cascades. Michaelis-Menten kinetics were associated to each reaction in order to tailor the different enzymes kinetics, creating a system of ordinary differential equations (ODEs). The data of this study offers a first tool to be considered in the therapeutic management of the NBM patient undergoing immunotherapeutic treatment.
AB - Immunotherapy is a promising new therapeutic approach for neuroblastoma (NBM): An anti-GD2 vaccine combined with orally administered soluble beta-glucan is undergoing a phase II clinical trial and nivolumab and ipilimumab are being tested in recurrent and refractory tumors. Unfortunately, predictive biomarkers of response to immunotherapy are currently not available for NBM patients. The aim of this study was to create a computational network model simulating the different intracellular pathways involved in NBM, in order to predict how the tumor phenotype may be influenced to increase the sensitivity to anti-programmed cell death-ligand-1 (PD-L1)/programmed cell death-1 (PD-1) immunotherapy. The model runs on COPASI software. In order to determine the influence of intracellular signaling pathways on the expression of PD-L1 in NBM, we first developed an integrated network of protein kinase cascades. Michaelis-Menten kinetics were associated to each reaction in order to tailor the different enzymes kinetics, creating a system of ordinary differential equations (ODEs). The data of this study offers a first tool to be considered in the therapeutic management of the NBM patient undergoing immunotherapeutic treatment.
KW - Computational modelling
KW - COPASI
KW - Immunotherapy
KW - Neuroblastoma
KW - PD-L1
UR - http://www.scopus.com/inward/record.url?scp=85073332261&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073332261&partnerID=8YFLogxK
U2 - 10.3390/brainsci9090221
DO - 10.3390/brainsci9090221
M3 - Article
AN - SCOPUS:85073332261
VL - 9
JO - Brain Sciences
JF - Brain Sciences
SN - 2076-3425
IS - 9
M1 - 221
ER -