Cooperation of Oncolytic Herpes Virotherapy and PD-1 Blockade in Murine Rhabdomyosarcoma Models

Abstract Oncolytic virotherapy is an effective immunotherapeutic approach for cancer treatment via a multistep process including direct tumor cell lysis, induction of cytotoxic or apoptosis-sensitizing cytokines and promotion of antitumor T cell responses. Solid tumors limit the effectiveness of imm...

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Autores principales:	Chun-Yu Chen, Pin-Yi Wang, Brian Hutzen, Les Sprague, Hayley M. Swain, Julia K. Love, Joseph R. Stanek, Louis Boon, Joe Conner, Timothy P. Cripe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fdcd41e11f1d41dba014f2f0f98645df
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spelling	oai:doaj.org-article:fdcd41e11f1d41dba014f2f0f98645df2021-12-02T15:05:07ZCooperation of Oncolytic Herpes Virotherapy and PD-1 Blockade in Murine Rhabdomyosarcoma Models10.1038/s41598-017-02503-82045-2322https://doaj.org/article/fdcd41e11f1d41dba014f2f0f98645df2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02503-8https://doaj.org/toc/2045-2322Abstract Oncolytic virotherapy is an effective immunotherapeutic approach for cancer treatment via a multistep process including direct tumor cell lysis, induction of cytotoxic or apoptosis-sensitizing cytokines and promotion of antitumor T cell responses. Solid tumors limit the effectiveness of immunotherapeutics in diverse ways such as secretion of immunosuppressive cytokines and expression of immune inhibitory ligands to inhibit antitumor T cell function. Blocking programmed cell death protein (PD)-1 signaling, which mediates T cell suppression via engagement of its inhibitory ligands, PD-L1 or PD-L2, is of particular interest due to recent successes in many types of cancer. In syngeneic murine rhabdomyosarcoma models, we found that M3-9-M (MHC I high) but not 76-9 (MHC I low) tumors respond to oncolytic herpes simplex virus-1 (oHSV-1) and PD-1 blockade combination therapy. In addition, the therapeutic outcomes in M3-9-M tumor models correlated with the increased incidence of CD4+ and CD8+ T cells but not with the CD4+CD25+Foxp3+ regulatory T cell populations in the tumor. Overall, our data suggest the combination of PD-1 blockade and oHSV-1 may be an effective treatment strategy for childhood soft tissue sarcoma.Chun-Yu ChenPin-Yi WangBrian HutzenLes SpragueHayley M. SwainJulia K. LoveJoseph R. StanekLouis BoonJoe ConnerTimothy P. CripeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chun-Yu Chen Pin-Yi Wang Brian Hutzen Les Sprague Hayley M. Swain Julia K. Love Joseph R. Stanek Louis Boon Joe Conner Timothy P. Cripe Cooperation of Oncolytic Herpes Virotherapy and PD-1 Blockade in Murine Rhabdomyosarcoma Models
description	Abstract Oncolytic virotherapy is an effective immunotherapeutic approach for cancer treatment via a multistep process including direct tumor cell lysis, induction of cytotoxic or apoptosis-sensitizing cytokines and promotion of antitumor T cell responses. Solid tumors limit the effectiveness of immunotherapeutics in diverse ways such as secretion of immunosuppressive cytokines and expression of immune inhibitory ligands to inhibit antitumor T cell function. Blocking programmed cell death protein (PD)-1 signaling, which mediates T cell suppression via engagement of its inhibitory ligands, PD-L1 or PD-L2, is of particular interest due to recent successes in many types of cancer. In syngeneic murine rhabdomyosarcoma models, we found that M3-9-M (MHC I high) but not 76-9 (MHC I low) tumors respond to oncolytic herpes simplex virus-1 (oHSV-1) and PD-1 blockade combination therapy. In addition, the therapeutic outcomes in M3-9-M tumor models correlated with the increased incidence of CD4+ and CD8+ T cells but not with the CD4+CD25+Foxp3+ regulatory T cell populations in the tumor. Overall, our data suggest the combination of PD-1 blockade and oHSV-1 may be an effective treatment strategy for childhood soft tissue sarcoma.
format	article
author	Chun-Yu Chen Pin-Yi Wang Brian Hutzen Les Sprague Hayley M. Swain Julia K. Love Joseph R. Stanek Louis Boon Joe Conner Timothy P. Cripe
author_facet	Chun-Yu Chen Pin-Yi Wang Brian Hutzen Les Sprague Hayley M. Swain Julia K. Love Joseph R. Stanek Louis Boon Joe Conner Timothy P. Cripe
author_sort	Chun-Yu Chen
title	Cooperation of Oncolytic Herpes Virotherapy and PD-1 Blockade in Murine Rhabdomyosarcoma Models
title_short	Cooperation of Oncolytic Herpes Virotherapy and PD-1 Blockade in Murine Rhabdomyosarcoma Models
title_full	Cooperation of Oncolytic Herpes Virotherapy and PD-1 Blockade in Murine Rhabdomyosarcoma Models
title_fullStr	Cooperation of Oncolytic Herpes Virotherapy and PD-1 Blockade in Murine Rhabdomyosarcoma Models
title_full_unstemmed	Cooperation of Oncolytic Herpes Virotherapy and PD-1 Blockade in Murine Rhabdomyosarcoma Models
title_sort	cooperation of oncolytic herpes virotherapy and pd-1 blockade in murine rhabdomyosarcoma models
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fdcd41e11f1d41dba014f2f0f98645df
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Cooperation of Oncolytic Herpes Virotherapy and PD-1 Blockade in Murine Rhabdomyosarcoma Models

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