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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]

Virotherapy combined with anti-PD-1 transiently reshapes the tumor immune environment and induces anti-tumor immunity in a preclinical PDAC model

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  • Media type: E-Article
  • Title: Virotherapy combined with anti-PD-1 transiently reshapes the tumor immune environment and induces anti-tumor immunity in a preclinical PDAC model
  • Contributor: 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]
  • Published: 2022
  • Published in: Frontiers in immunology ; 13(2022), Artikel-ID 1096162, Seite 1-16
  • Language: English
  • DOI: 10.3389/fimmu.2022.1096162
  • Identifier:
  • Origination:
  • Footnote: Elektronische Reproduktion der Druck-Ausgabe 16. Januar 2023
  • Description: 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.
  • Access State: Open Access