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

oleh: Rūta Veinalde, Gemma Pidelaserra-Martí, Gemma Pidelaserra-Martí, Gemma Pidelaserra-Martí, Coline Moulin, Coline Moulin, Chin Leng Tan, Chin Leng Tan, Theresa E. Schäfer, Na Kang, Claudia R. Ball, Claudia R. Ball, Jonas Leichsenring, Jonas Leichsenring, Albrecht Stenzinger, Lars Kaderali, Dirk Jäger, Dirk Jäger, Guy Ungerechts, Guy Ungerechts, Christine E. Engeland, Christine E. Engeland, Christine E. Engeland

Format: Article
Diterbitkan: Frontiers Media S.A. 2023-01-01

Deskripsi

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.