TY  - JOUR
AU  - Veinalde, Ruta
AU  - Pidelaserra-Martí, Gemma
AU  - Moulin, Coline
AU  - Tan, Chin Leng
AU  - Schäfer, Theresa
AU  - Kang, Na
AU  - Ball, Claudia R
AU  - Leichsenring, Jonas
AU  - Stenzinger, Albrecht
AU  - Kaderali, Lars
AU  - Jäger, Dirk
AU  - Ungerechts, Guy
AU  - Engeland, Christine
TI  - Virotherapy combined with anti-PD-1 transiently reshapes the tumor immune environment and induces anti-tumor immunity in a preclinical PDAC model.
JO  - Frontiers in immunology
VL  - 13
SN  - 1664-3224
CY  - Lausanne
PB  - Frontiers Media
M1  - DKFZ-2023-00266
SP  - 1096162
PY  - 2023
N1  - #EA:F230#LA:F230#
AB  - 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.
KW  - Mice
KW  - Animals
KW  - Pancreatic Neoplasms: pathology
KW  - Carcinoma, Pancreatic Ductal: genetics
KW  - Immunotherapy: methods
KW  - Oncolytic Virotherapy: methods
KW  - PD-1 (Other)
KW  - PDAC (Other)
KW  - cancer immunotherapy (Other)
KW  - immune checkpoint (Other)
KW  - measles vaccine (Other)
KW  - oncolytic virus (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36726983
C2  - pmc:PMC9886093
DO  - DOI:10.3389/fimmu.2022.1096162
UR  - https://inrepo02.dkfz.de/record/241158
ER  -