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@ARTICLE{Veinalde:241158,
author = {R. Veinalde$^*$ and G. Pidelaserra-Martí$^*$ and C. Moulin
and C. L. Tan$^*$ and T. Schäfer$^*$ and N. Kang and C. R.
Ball and J. Leichsenring and A. Stenzinger and L. Kaderali
and D. Jäger$^*$ and G. Ungerechts$^*$ and C. Engeland$^*$},
title = {{V}irotherapy combined with anti-{PD}-1 transiently
reshapes the tumor immune environment and induces anti-tumor
immunity in a preclinical {PDAC} model.},
journal = {Frontiers in immunology},
volume = {13},
issn = {1664-3224},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DKFZ-2023-00266},
pages = {1096162},
year = {2023},
note = {#EA:F230#LA:F230#},
abstract = {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.},
keywords = {Mice / Animals / Pancreatic Neoplasms: pathology /
Carcinoma, Pancreatic Ductal: genetics / Immunotherapy:
methods / Oncolytic Virotherapy: methods / PD-1 (Other) /
PDAC (Other) / cancer immunotherapy (Other) / immune
checkpoint (Other) / measles vaccine (Other) / oncolytic
virus (Other)},
cin = {F230 / D170 / D120},
ddc = {610},
cid = {I:(DE-He78)F230-20160331 / I:(DE-He78)D170-20160331 /
I:(DE-He78)D120-20160331},
pnm = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
pid = {G:(DE-HGF)POF4-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36726983},
pmc = {pmc:PMC9886093},
doi = {10.3389/fimmu.2022.1096162},
url = {https://inrepo02.dkfz.de/record/241158},
}