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Article

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

1
Children Oncohematology Foundation, 28079 Madrid, Spain
2
Department of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain
3
Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L’Hospitalet de Llobregat, 08908 Barcelona, Spain
4
Biomedical Research Foundation, Niño Jesús Children Hospital, 28009 Madrid, Spain
5
La Princesa Institute of Health Research, 28006 Madrid, Spain
6
Oncohematology Unit, Hospital Infantil Universitario Niño Jesús, 28009 Madrid, Spain
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(5), 1104; https://doi.org/10.3390/cancers12051104
Received: 2 April 2020 / Revised: 25 April 2020 / Accepted: 26 April 2020 / Published: 28 April 2020
(This article belongs to the Special Issue The Role of Adenovirus in Cancer Therapy)
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 Celyvir (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 Celyvir 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. View Full-Text
Keywords: neuroblastoma; oncolytic virotherapy; T lymphocytes (TILs); bioinformatic analysis; immune landscape neuroblastoma; oncolytic virotherapy; T lymphocytes (TILs); bioinformatic analysis; immune landscape
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MDPI and ACS Style

Franco-Luzón, L.; García-Mulero, S.; Sanz-Pamplona, R.; Melen, G.; Ruano, D.; Lassaletta, Á.; Madero, L.; González-Murillo, Á.; Ramírez, M. Genetic and Immune Changes Associated with Disease Progression under the Pressure of Oncolytic Therapy in A Neuroblastoma Outlier Patient. Cancers 2020, 12, 1104. https://doi.org/10.3390/cancers12051104

AMA Style

Franco-Luzón L, García-Mulero S, Sanz-Pamplona R, Melen G, Ruano D, Lassaletta Á, Madero L, González-Murillo Á, Ramírez M. Genetic and Immune Changes Associated with Disease Progression under the Pressure of Oncolytic Therapy in A Neuroblastoma Outlier Patient. Cancers. 2020; 12(5):1104. https://doi.org/10.3390/cancers12051104

Chicago/Turabian Style

Franco-Luzón, Lidia, Sandra García-Mulero, Rebeca Sanz-Pamplona, Gustavo Melen, David Ruano, Álvaro Lassaletta, Luís Madero, África González-Murillo, and Manuel Ramírez. 2020. "Genetic and Immune Changes Associated with Disease Progression under the Pressure of Oncolytic Therapy in A Neuroblastoma Outlier Patient" Cancers 12, no. 5: 1104. https://doi.org/10.3390/cancers12051104

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