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Cooperation of Oncolytic Herpes Virotherapy and PD-1 Blockade in Murine Rhabdomyosarcoma Models.
- Source :
-
Scientific reports [Sci Rep] 2017 May 24; Vol. 7 (1), pp. 2396. Date of Electronic Publication: 2017 May 24. - Publication Year :
- 2017
-
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 <superscript>+</superscript> and CD8 <superscript>+</superscript> T cells but not with the CD4 <superscript>+</superscript> CD25 <superscript>+</superscript> Foxp3 <superscript>+</superscript> 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.
- Subjects :
- Animals
CD8-Positive T-Lymphocytes drug effects
CD8-Positive T-Lymphocytes immunology
Cytokines genetics
Cytokines immunology
Dendritic Cells drug effects
Dendritic Cells immunology
Female
Gene Expression
Injections, Intralesional
Injections, Intraperitoneal
Mice
Mice, Inbred C57BL
Neoplasms, Experimental
Programmed Cell Death 1 Receptor genetics
Programmed Cell Death 1 Receptor immunology
Rhabdomyosarcoma genetics
Rhabdomyosarcoma immunology
Rhabdomyosarcoma mortality
Survival Analysis
T-Lymphocytes, Regulatory drug effects
T-Lymphocytes, Regulatory immunology
Antibodies, Monoclonal pharmacology
Combined Modality Therapy methods
Oncolytic Virotherapy methods
Programmed Cell Death 1 Receptor antagonists & inhibitors
Rhabdomyosarcoma therapy
Simplexvirus physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28539588
- Full Text :
- https://doi.org/10.1038/s41598-017-02503-8