Oncolytic virotherapy enhances the efficacy of a cancer vaccine by modulating the tumor microenvironment.
Animals
Cancer Vaccines
/ administration & dosage
Cell Line, Tumor
Combined Modality Therapy
Female
Glycoproteins
/ genetics
Humans
Lymphocytic choriomeningitis virus
/ genetics
Melanoma, Experimental
/ immunology
Mice
Oncolytic Virotherapy
/ methods
Oncolytic Viruses
/ physiology
Ovalbumin
/ immunology
Treatment Outcome
Tumor Microenvironment
/ drug effects
Vesicular stomatitis Indiana virus
/ metabolism
Viral Proteins
/ genetics
Xenograft Model Antitumor Assays
CD8 T cells
DC-based immunotherapy
melanoma
oncolytic virotherapy
tumor microenvironment
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 10 2019
01 10 2019
Historique:
received:
13
11
2018
accepted:
18
03
2019
pubmed:
12
4
2019
medline:
18
1
2020
entrez:
12
4
2019
Statut:
ppublish
Résumé
The efficacy of cancer vaccines has been limited by the immunosuppressive tumor microenvironment, which can be alleviated by immune checkpoint inhibitor (ICI) therapy. Here, we tested if oncolytic viruses (OVs), similar to ICI, can also synergize with cancer vaccines by modulating the tumor microenvironment. VSV-GP, a chimeric vesicular stomatitis virus (VSV) pseudotyped with the glycoprotein (GP) of the lymphocytic choriomeningitis virus, is a promising new OV candidate. Here, we show that in mouse B16-OVA melanoma, combination treatment of VSV-GP with an ovalbumin (OVA) peptide-loaded dendritic cell (DC) vaccine (DCVacc) significantly enhanced survival over the single agent therapies, although both DCVacc and DCVacc/VSV-GP treatments induced comparable levels of OVA-specific CD8 T cell responses. Virus replication was minimal so that direct viral oncolysis in B16-OVA did not contribute to this synergism. The strong therapeutic effect of the DCVacc/VSV-GP combination treatment was associated with high numbers of tumor-infiltrating, highly activated T cells and the relative reduction of regulatory T cells in treated and contra-lateral nontreated tumors. Accordingly, depletion of CD8 T cells but not natural killer cells abrogated the therapeutic effect of DCVacc/VSV-GP supporting the crucial role of CD8 T cells. In addition, a drastic increase in several proinflammatory cytokines was observed in VSV-GP-treated tumors. Taken together, OVs, similar to ICI, have the potential to markedly increase the efficacy of cancer vaccines by alleviating local immune suppression in the tumor microenvironment.
Identifiants
pubmed: 30972741
doi: 10.1002/ijc.32325
pmc: PMC6767478
doi:
Substances chimiques
Cancer Vaccines
0
Glycoproteins
0
Viral Proteins
0
Ovalbumin
9006-59-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1958-1969Informations de copyright
© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
Références
J Virol. 2011 Dec;85(23):12160-9
pubmed: 21917977
Clin Cancer Res. 2004 Jan 15;10(2):521-30
pubmed: 14760073
Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):351-8
pubmed: 11773639
Cancer Immunol Immunother. 2012 Oct;61(10):1791-804
pubmed: 22426890
Br J Cancer. 2011 Jun 28;105(1):93-103
pubmed: 21629244
N Engl J Med. 2003 Jan 16;348(3):203-13
pubmed: 12529460
Science. 2006 Sep 29;313(5795):1960-4
pubmed: 17008531
Mol Ther. 2008 Jan;16(1):146-53
pubmed: 18071337
Eur J Nucl Med Mol Imaging. 2005 Jul;32(7):731-41
pubmed: 15924229
Hum Gene Ther. 2008 Jun;19(6):635-47
pubmed: 18533893
Clin Cancer Res. 2008 Nov 15;14(22):7358-66
pubmed: 19010851
J Immunother. 2010 Feb-Mar;33(2):115-25
pubmed: 20145551
Adv Immunol. 2010;108:111-65
pubmed: 21056730
Cancer Res. 2010 Jun 1;70(11):4539-49
pubmed: 20484025
J Immunol Methods. 1999 Feb 1;223(1):77-92
pubmed: 10037236
Immunol Cell Biol. 2010 May-Jun;88(4):424-30
pubmed: 20368713
Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4275-80
pubmed: 20160101
Cancer Res. 2014 Jul 1;74(13):3567-78
pubmed: 24812275
J Transl Med. 2012 Oct 03;10:205
pubmed: 23034130
J Virol. 2002 Jan;76(2):895-904
pubmed: 11752178
J Clin Invest. 1999 Jul;104(2):173-80
pubmed: 10411546
Mol Ther. 2011 Feb;19(2):335-44
pubmed: 21119618
Lancet Oncol. 2014 Jun;15(7):e257-67
pubmed: 24872109
Nat Rev Cancer. 2005 Apr;5(4):263-74
pubmed: 15776005
Immunity. 2013 Jul 25;39(1):61-73
pubmed: 23890064
J Virol. 2014 May;88(9):4897-907
pubmed: 24554655
Trends Immunol. 2017 Aug;38(8):577-593
pubmed: 28610825
Oncoimmunology. 2016 Mar 16;5(6):e1160193
pubmed: 27471635
Immunity. 2013 Jul 25;39(1):38-48
pubmed: 23890062
Front Oncol. 2014 Apr 10;4:74
pubmed: 24782985
Hum Gene Ther. 2010 Apr;21(4):439-50
pubmed: 19922169
J Clin Invest. 2000 Mar;105(6):R9-R14
pubmed: 10727452
Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18538-43
pubmed: 16344461
Mol Ther Oncolytics. 2016 Sep 28;3:16021
pubmed: 27738655
JCI Insight. 2017 Apr 20;2(8):null
pubmed: 28422751
Cancer Immunol Immunother. 2009 Mar;58(3):449-59
pubmed: 18791714
Cancer Res. 1999 Jan 1;59(1):56-8
pubmed: 9892184
Oncotarget. 2017 Jun 27;8(40):67439-67456
pubmed: 28978044
J Clin Invest. 2006 Jul;116(7):1935-45
pubmed: 16778987
Cancer Res. 2007 Mar 15;67(6):2840-8
pubmed: 17363607
Gene Ther. 2010 Feb;17(2):158-70
pubmed: 20016540
J Virol. 2011 Jun;85(11):5679-84
pubmed: 21450833
Nature. 2017 Jan 18;541(7637):321-330
pubmed: 28102259
J Exp Med. 2002 May 20;195(10):1279-88
pubmed: 12021308
Immunology. 2001 Apr;102(4):486-97
pubmed: 11328383
J Immunol. 2014 Mar 1;192(5):2514-21
pubmed: 24477907
Biomedicines. 2017 Feb 10;5(1):
pubmed: 28536351