STAT3 Contributes To Oncolytic Newcastle Disease Virus-Induced Immunogenic Cell Death in Melanoma Cells.

STAT3 Contributes To Oncolytic Newcastle Disease Virus-Induced Immunogenic Cell Death in Melanoma Cells.

Publication date: Jan 29, 2019

Background: Oncolytic viruses (OVs) are emerging as potent inducers of immunogenic cell death (ICD), releasing danger-associated molecular patterns (DAMPs) that induce potent anticancer immunity. Oncolytic Newcastle disease virus (NDV) has been shown to educe ICD in both glioma and lung cancer cells. The objective of this study is to investigate whether oncolytic NDV induces ICD in melanoma cells and how it is regulated. Methods: Various time points were actuated to check the expression and release of ICD markers induced by NDV strain, NDV/FMW in melanoma cell lines. The expression and release of ICD markers induced by oncolytic NDV strain, NDV/FMW, in melanoma cell lines at various time points were determined. Surface-exposed calreticulin (CRT) was inspected by confocal imaging. The supernatants of NDV/FMW infected cells were collected and concentrated for the determination of ATP secretion by ELISA, HMGB1, and HSP70/90 expression by immunoblot (IB) analysis. Pharmacological inhibition of apoptosis, autophagy, necroptosis, ER Stress, and STAT3 (signal transducer and activator of transcription 3) was achieved by treatment with small molecule inhibitors. Melanoma cell lines stably depleted of STAT3 were established with lentiviral constructs. Supernatants from NDV-infected cells were intratumorally injected to mice bearing melanoma cells-derived tumors. Results: Oncolytic NDV induced CRT exposure, the release of HMGB1 and HSP70/90 as well as secretion of ATP in melanoma cells. Inhibition of apoptosis, autophagy, necroptosis or ER stress attenuated NDV/FMW-induced release of HMGB1 and HSP70/90. Moreover, NDV/FMW-induced ICD markers in melanoma cells were also suppressed by either treatment with a STAT3 inhibitor or shRNA-mediated depletion of STAT3. Of translational importance, treatment of mice bearing melanoma cells-derived tumors with supernatants from NDV/FMW-infected cells significantly inhibited tumor growth. Conclusions: Our data authenticate that oncolytic NDV/FMW might be a potent inducer of ICD in melanoma cells, which is amalgamated with several forms of cell death. We also show that STAT3 plays a role in NDV/FMW-induced ICD in melanoma cells. Together, our data highlight oncolytic NDV as propitious for cancer therapeutics by stimulatingan anti-melanoma immune response.

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Shao, X., Wang, X., Guo, X., Jiang, K., Ye, T., Chen, J., Fang, J., Gu, L., Wang, S., Zhang, G., Meng, S., and Xu, Q. STAT3 Contributes To Oncolytic Newcastle Disease Virus-Induced Immunogenic Cell Death in Melanoma Cells. 23763. 2019 Front Oncol (9):

Concepts Keywords
Apoptosis Oncolytic virus
ATP Biotechnology
Autophagy Experimental cancer treatments
Calreticulin Transcription factors
Confocal Branches of biology
CRT ICD melanoma
ELISA Tumors
Glioma Educe ICD glioma
HSP70 ICD markers melanoma
Immune Response Tumor
Immunity ATP melanoma
Immunoblot Confocal imaging supernatants
Immunogenic HMGB1
Inducer Apoptosis
Inhibitor Apoptosis
Lentiviral Melanoma
Lung NDV
Melanoma Proteins
Newcastle Virotherapy
Oncolytic Viruses
Small Molecule


Type Source Name
disease DOID cancer
disease MESH growth
disease MESH tumors
pathway BSID Release
disease DOID lung cancer
disease MESH lung cancer
pathway BSID Glioma
disease MESH glioma
pathway BSID Melanoma
disease DOID Melanoma
disease MESH Melanoma
disease DOID Newcastle Disease
disease MESH Newcastle Disease


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