Targeting STAT3 enhances NDV-induced immunogenic cell death in prostate cancer cells

Area of Science:

• Oncology
• Virology
• Immunology

Background:

• Oncolytic viruses like Newcastle disease virus (NDV) can induce immunogenic cell death (ICD).
• ICD releases danger-associated molecular patterns (DAMPs) that stimulate anti-tumor immunity.
• Prostate cancer remains a significant health challenge, necessitating novel therapeutic strategies.

Purpose of the Study:

• To investigate if and how oncolytic NDV triggers ICD in prostate cancer cells.
• To identify the specific ICD markers released by NDV-infected prostate cancer cells.
• To explore the potential of combining oncolytic NDV with STAT3 inhibition for enhanced anti-cancer effects.

Main Methods:

• Infection of prostate cancer cells with oncolytic NDV strain FMW.
• Assessment of ICD markers: calreticulin (CRT), heat shock proteins (HSP70/90), and high-mobility group box 1 (HMGB1).
• Pharmacological inhibition of apoptosis, necroptosis, autophagy, and ER stress.
• STAT3 inhibition via a chemical inhibitor or shRNA.
• Tumor growth assessment in nude mice bearing prostate cancer xenografts.

Main Results:

• NDV/FMW infection induced expression and release of CRT, HSP70/90, and HMGB1 in prostate cancer cells.
• Modulation of apoptosis, necroptosis, autophagy, or ER stress affected HMGB1 and HSP70/90 release.
• STAT3 inhibition, either pharmacologically or via shRNA, enhanced NDV-induced ICD markers.
• Tumors in mice treated with supernatants from NDV-infected cells showed reduced growth compared to controls.

Conclusions:

• Oncolytic NDV effectively induces ICD markers in prostate cancer cells.
• STAT3 signaling pathway plays a role in modulating NDV-induced ICD.
• Combination therapy of oncolytic NDV and STAT3 inhibition shows promise for improving anti-prostate cancer efficacy.