Virotherapy combined with anti-PD-1 transiently reshapes the tumor immune environment and induces anti-tumor immunity in a preclinical PDAC model.
PD-1
PDAC
cancer immunotherapy
immune checkpoint
measles vaccine
oncolytic virus
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
11
11
2022
accepted:
12
12
2022
entrez:
2
2
2023
pubmed:
3
2
2023
medline:
4
2
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36726983
doi: 10.3389/fimmu.2022.1096162
pmc: PMC9886093
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1096162Informations de copyright
Copyright © 2023 Veinalde, Pidelaserra-Martí, Moulin, Tan, Schäfer, Kang, Ball, Leichsenring, Stenzinger, Kaderali, Jäger, Ungerechts and Engeland.
Déclaration de conflit d'intérêts
GU is co-founder, stakeholder and CMO/CSO of CanVirex AG, a company developing oncolytic viruses as cancer immunotherapeutics. RV, GU, and CE are listed as inventors on a patent related to application of oncolytic viruses as cancer immunotherapy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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