TY - JOUR
T1 - Newcastle Disease Virus (NDV) Oncolytic Activity in Human Glioma Tumors Is Dependent on CDKN2A-Type I IFN Gene Cluster Codeletion
AU - García-Romero, Noemi
AU - Palacín-Aliana, Irina
AU - Esteban-Rubio, Susana
AU - Madurga, Rodrigo
AU - Rius-Rocabert, Sergio
AU - Carrión-Navarro, Josefa
AU - Presa, Jesús
AU - Cuadrado-Castano, Sara
AU - Sánchez-Gómez, Pilar
AU - García-Sastre, Adolfo
AU - Nistal-Villan, Estanislao
AU - Ayuso-Sacido, Angel
N1 - Funding Information:
This work was supported by grants from the Secrétariat d’Etat à la Recherche Scientifique et à la Technologie (SERST), Tunisia. We thank M. Mnari from INRAT for providing the PVYO inoculum, and Mr. Ayadi Hajji from ENIS for help with English.
PY - 2020/6/5
Y1 - 2020/6/5
N2 - Glioblastoma (GBM) is the most aggressive and frequent primary brain tumor in adults with a median overall survival of 15 months. Tumor recurrence and poor prognosis are related to cancer stem cells (CSCs), which drive resistance to therapies. A common characteristic in GBM is CDKN2A gene loss, located close to the cluster of type I IFN genes at Ch9p21. Newcastle disease virus (NDV) is an avian paramyxovirus with oncolytic and immunostimulatory properties that has been proposed for the treatment of GBM. We have analyzed the CDKN2A-IFN I gene cluster in 1018 glioma tumors and evaluated the NDV oncolytic effect in six GBM CSCs ex vivo and in a mouse model. Our results indicate that more than 50% of GBM patients have some IFN deletion. Moreover, GBM susceptibility to NDV is dependent on the loss of the type I IFN. Infection of GBM with an NDV-expressing influenza virus NS1 protein can overcome the resistance to oncolysis by NDV of type I-competent cells. These results highlight the potential of using NDV vectors in antitumor therapies.
AB - Glioblastoma (GBM) is the most aggressive and frequent primary brain tumor in adults with a median overall survival of 15 months. Tumor recurrence and poor prognosis are related to cancer stem cells (CSCs), which drive resistance to therapies. A common characteristic in GBM is CDKN2A gene loss, located close to the cluster of type I IFN genes at Ch9p21. Newcastle disease virus (NDV) is an avian paramyxovirus with oncolytic and immunostimulatory properties that has been proposed for the treatment of GBM. We have analyzed the CDKN2A-IFN I gene cluster in 1018 glioma tumors and evaluated the NDV oncolytic effect in six GBM CSCs ex vivo and in a mouse model. Our results indicate that more than 50% of GBM patients have some IFN deletion. Moreover, GBM susceptibility to NDV is dependent on the loss of the type I IFN. Infection of GBM with an NDV-expressing influenza virus NS1 protein can overcome the resistance to oncolysis by NDV of type I-competent cells. These results highlight the potential of using NDV vectors in antitumor therapies.
KW - Interferon I
KW - Newcastle disease virus (NDV)
KW - glioblastoma
KW - oncolytic virotherapy
UR - http://www.scopus.com/inward/record.url?scp=85086355561&partnerID=8YFLogxK
U2 - 10.3390/cells9061405
DO - 10.3390/cells9061405
M3 - Article
C2 - 32516884
AN - SCOPUS:85086355561
SN - 2073-4409
VL - 9
JO - Cells
JF - Cells
IS - 6
M1 - 1420
ER -