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| Home > Publications database > Virotherapy combined with anti-PD-1 transiently reshapes the tumor immune environment and induces anti-tumor immunity in a preclinical PDAC model. |
| Home > Publications database > Virotherapy combined with anti-PD-1 transiently reshapes the tumor immune environment and induces anti-tumor immunity in a preclinical PDAC model. |
| Journal Article | DKFZ-2023-00266 |
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2023
Frontiers Media
Lausanne
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Please use a persistent id in citations: doi:10.3389/fimmu.2022.1096162
Abstract: Pancreatic ductal adenocarcinoma (PDAC) is largely refractory to cancer immunotherapy with PD-1 immune checkpoint blockade (ICB). Oncolytic virotherapy has been shown to synergize with ICB. In this work, we investigated the combination of anti-PD-1 and oncolytic measles vaccine in an immunocompetent transplantable PDAC mouse model.We characterized tumor-infiltrating T cells by immunohistochemistry, flow cytometry and T cell receptor sequencing. Further, we performed gene expression profiling of tumor samples at baseline, after treatment, and when tumors progressed. Moreover, we analyzed systemic anti-tumor and anti-viral immunity.Combination treatment significantly prolonged survival compared to monotherapies. Tumor-infiltrating immune cells were increased after virotherapy. Gene expression profiling revealed a unique, but transient signature of immune activation after combination treatment. However, systemic anti-tumor immunity was induced by virotherapy and remained detectable even when tumors progressed. Anti-PD-1 treatment did not impact anti-viral immunity.Our results indicate that combined virotherapy and ICB induces anti-tumor immunity and reshapes the tumor immune environment. However, further refinement of this approach may be required to develop its full potential and achieve durable efficacy.
Keyword(s): Mice (MeSH) ; Animals (MeSH) ; Pancreatic Neoplasms: pathology (MeSH) ; Carcinoma, Pancreatic Ductal: genetics (MeSH) ; Immunotherapy: methods (MeSH) ; Oncolytic Virotherapy: methods (MeSH) ; PD-1 ; PDAC ; cancer immunotherapy ; immune checkpoint ; measles vaccine ; oncolytic virus
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