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Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy

Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an oncolytic poxvirus would attract T cells into the tumour, and induce PD-L1 expression in cancer and immune cells, lea...

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Autores principales: Liu, Zuqiang, Ravindranathan, Roshni, Kalinski, Pawel, Guo, Z. Sheng, Bartlett, David L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378974/
https://www.ncbi.nlm.nih.gov/pubmed/28345650
http://dx.doi.org/10.1038/ncomms14754
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author Liu, Zuqiang
Ravindranathan, Roshni
Kalinski, Pawel
Guo, Z. Sheng
Bartlett, David L.
author_facet Liu, Zuqiang
Ravindranathan, Roshni
Kalinski, Pawel
Guo, Z. Sheng
Bartlett, David L.
author_sort Liu, Zuqiang
collection PubMed
description Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an oncolytic poxvirus would attract T cells into the tumour, and induce PD-L1 expression in cancer and immune cells, leading to more susceptible targets for anti-PD-L1 immunotherapy. Our results demonstrate in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector T cells and induces PD-L1 expression on both cancer and immune cells in the tumour. The dual therapy reduces PD-L1(+) cells and facilitates non-redundant tumour infiltration of effector CD8(+), CD4(+) T cells, with increased IFN-γ, ICOS, granzyme B and perforin expression. Furthermore, the treatment reduces the virus-induced PD-L1(+) DC, MDSC, TAM and Treg, as well as co-inhibitory molecules-double-positive, severely exhausted PD-1(+)CD8(+) T cells, leading to reduced tumour burden and improved survival. This combinatorial therapy may be applicable to a much wider population of cancer patients.
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spelling pubmed-53789742017-04-11 Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy Liu, Zuqiang Ravindranathan, Roshni Kalinski, Pawel Guo, Z. Sheng Bartlett, David L. Nat Commun Article Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an oncolytic poxvirus would attract T cells into the tumour, and induce PD-L1 expression in cancer and immune cells, leading to more susceptible targets for anti-PD-L1 immunotherapy. Our results demonstrate in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector T cells and induces PD-L1 expression on both cancer and immune cells in the tumour. The dual therapy reduces PD-L1(+) cells and facilitates non-redundant tumour infiltration of effector CD8(+), CD4(+) T cells, with increased IFN-γ, ICOS, granzyme B and perforin expression. Furthermore, the treatment reduces the virus-induced PD-L1(+) DC, MDSC, TAM and Treg, as well as co-inhibitory molecules-double-positive, severely exhausted PD-1(+)CD8(+) T cells, leading to reduced tumour burden and improved survival. This combinatorial therapy may be applicable to a much wider population of cancer patients. Nature Publishing Group 2017-03-27 /pmc/articles/PMC5378974/ /pubmed/28345650 http://dx.doi.org/10.1038/ncomms14754 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Liu, Zuqiang
Ravindranathan, Roshni
Kalinski, Pawel
Guo, Z. Sheng
Bartlett, David L.
Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy
title Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy
title_full Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy
title_fullStr Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy
title_full_unstemmed Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy
title_short Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy
title_sort rational combination of oncolytic vaccinia virus and pd-l1 blockade works synergistically to enhance therapeutic efficacy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378974/
https://www.ncbi.nlm.nih.gov/pubmed/28345650
http://dx.doi.org/10.1038/ncomms14754
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