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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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Main Authors: Veinalde, Rūta (Author) , Pidelaserra Martí, Gemma (Author) , Moulin, Coline (Author) , Tan, Chin Leng (Author) , Schäfer, Theresa E. (Author) , Kang, Na (Author) , Ball, Claudia R. (Author) , Leichsenring, Jonas (Author) , Stenzinger, Albrecht (Author) , Kaderali, Lars (Author) , Jäger, Dirk (Author) , Ungerechts, Guy (Author) , Engeland, Christine Elisabeth (Author)
Format: Article (Journal)
Language:English
Published: 2022
In: Frontiers in immunology
Year: 2022, Volume: 13, Pages: 1-16
ISSN:1664-3224
DOI:10.3389/fimmu.2022.1096162
Online Access: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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Author Notes: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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Summary: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.
Item Description:Elektronische Reproduktion der Druck-Ausgabe 16. Januar 2023
Gesehen am 31.01.2023
Physical Description:Online Resource
ISSN:1664-3224
DOI:10.3389/fimmu.2022.1096162

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