%0 Journal Article
%A Veinalde, Ruta
%A Pidelaserra-Martí, Gemma
%A Moulin, Coline
%A Tan, Chin Leng
%A Schäfer, Theresa
%A Kang, Na
%A Ball, Claudia R
%A Leichsenring, Jonas
%A Stenzinger, Albrecht
%A Kaderali, Lars
%A Jäger, Dirk
%A Ungerechts, Guy
%A Engeland, Christine
%T Virotherapy combined with anti-PD-1 transiently reshapes the tumor immune environment and induces anti-tumor immunity in a preclinical PDAC model.
%J Frontiers in immunology
%V 13
%@ 1664-3224
%C Lausanne
%I Frontiers Media
%M DKFZ-2023-00266
%P 1096162
%D 2023
%Z #EA:F230#LA:F230#
%X 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.
%K Mice
%K Animals
%K Pancreatic Neoplasms: pathology
%K Carcinoma, Pancreatic Ductal: genetics
%K Immunotherapy: methods
%K Oncolytic Virotherapy: methods
%K PD-1 (Other)
%K PDAC (Other)
%K cancer immunotherapy (Other)
%K immune checkpoint (Other)
%K measles vaccine (Other)
%K oncolytic virus (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:36726983
%2 pmc:PMC9886093
%R 10.3389/fimmu.2022.1096162
%U https://inrepo02.dkfz.de/record/241158