Effects of oncolytic immunotherapy with RP1 (vusolimogene oderparepvec) on immune cells mediate responsiveness to anti-PD-1 via STING-mediated interferon signaling

作者：Victoria Roulstone, Joan Kyula, Elizabeth Appleton, Praveen K. Bommareddy, Anton Patrikeev, Sylwia Jones, Linta Kuncheria, Charleen ML Chan Wah Hak, Shane Siang Chin Foo, Holly Baldock, Amarin Wongariyapak, Isla Leslie, Robert J. Pickering, Christian Zierhut, Henry G Smith, Nitya Mohan, Carmen Murano, Lisa C. Hubbard, Isaac Dean, Emmanuel C. Patin, Jim Gkantalis, David Mansfield, Malin Pedersen, Martin McLaughlin, Maria Goicoechea, Scott Layzell, Jonathan Mannion, Winnie Fernando, Pascal Meier, Richard Vile, Alan Melcher, Robert S. Coffin, Kevin J Harrington · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2026 · DOI：10.1136/jitc-2025-013692 · 被引用次数：1 · 研究领域：interferon and immune responses、Virus-based gene therapy research、Cancer Research and Treatments

BACKGROUND: Antitumor immune responses induced by oncolytic immunotherapy (OI) are often followed by upregulation of programmed death-ligand 1 (PD-L1). As such, the combination of OI with blockade of the programmed cell death protein-1 (PD-1)/PD-L1 axis has demonstrated therapeutic activity in preclinical and clinical trials. The purpose of this study is to understand further the immune-mediated mechanism of interaction between oncolytic viruses and anti-PD-1 therapy. METHODS: Tumor cells and immune cells (splenocytes) were cultured separately, or in co-culture with vusolimogene oderparepvec, an oncolytic herpes simplex virus expressing the fusogenic gibbon-ape leukemia virus-fusogenic membrane glycoprotein protein (GALV) and granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as RP1. Viral replication, interferon (IFN) responses and PD-L1 expression were analyzed using wild-type, IFNAR1, TNFAR1 and STING knockout splenocytes. In vivo studies evaluated immune cell infiltrates into the tumor following RP1 administration with anti-PD-1 therapy. RESULTS: RP1 replication was evident in tumor cells but not splenocytes. This was also accompanied by upregulated IFN expression in cultured splenocytes that was absent in cultured tumor cells. However, when these cell types were co-cultured, splenocytes mediated an interferon response to RP1 via STING that was transmitted to tumor cells in a non-touch-dependent manner. Tumor cells responded to these input signals via u...