Virotherapy combined with anti-PD-1 transiently reshapes the tumor immune environment and induces anti-tumor immunity in a preclinical PDAC model
IntroductionPancreatic 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 imm...
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| Hauptverfasser: | , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2022
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| In: |
Frontiers in immunology
Year: 2022, Jahrgang: 13, Pages: 1-16 |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2022.1096162 |
| Online-Zugang: | Resolving-System, kostenfrei, Volltext: https://doi.org/10.3389/fimmu.2022.1096162 Verlag, kostenfrei, Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2022.1096162 
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| Verfasserangaben: | Rūta Veinalde, Gemma Pidelaserra-Martí, Coline Moulin, Chin Leng Tan, Theresa E. Schäfer, Na Kang, Claudia R. Ball, Jonas Leichsenring, Albrecht Stenzinger, Lars Kaderali, Dirk Jäger, Guy Ungerechts, Christine E. Engeland |
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| 520 | |a IntroductionPancreatic 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.MethodsWe 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.ResultsCombination 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.DiscussionOur 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. | ||
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