Genetic and Immune Changes Associated with Disease Progression under the Pressure of Oncolytic Therapy in A Neuroblastoma Outlier Patient

Little is known about the effect of oncolytic adenovirotherapy on pediatric tumors. Here we present the clinical case of a refractory neuroblastoma that responded positively to (ICOVIR-5 oncolytic adenovirus delivered by autologous mesenchymal stem cells) for several months. We analyzed samples duri...

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Published inCancers Vol. 12; no. 5; p. 1104
Main Authors Franco-Luzón, Lidia, García-Mulero, Sandra, Sanz-Pamplona, Rebeca, Melen, Gustavo, Ruano, David, Lassaletta, Álvaro, Madero, Luís, González-Murillo, África, Ramírez, Manuel
Format Journal Article
LanguageEnglish
Published Switzerland MDPI 28.04.2020
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Summary:Little is known about the effect of oncolytic adenovirotherapy on pediatric tumors. Here we present the clinical case of a refractory neuroblastoma that responded positively to (ICOVIR-5 oncolytic adenovirus delivered by autologous mesenchymal stem cells) for several months. We analyzed samples during tumor evolution in order to identify molecular and mutational features that could explain the interactions between treatment and tumor and how the balance between both of them evolved. We identified a higher adaptive immune infiltration during stabilized disease compared to progression, and also a higher mutational rate and T-cell receptor (TCR) diversity during disease progression. Our results indicate an initial active role of the immune system controlling tumor growth during therapy. The tumor eventually escaped from the control exerted by virotherapy through acquisition of resistance by the tumor microenvironment that exhausted the initial T cell response.
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ISSN:2072-6694
2072-6694
DOI:10.3390/cancers12051104