TNFa and IL2 Encoding Oncolytic Adenovirus Activates Pathogen and Danger-Associated Immunological Signaling.
Adenoviridae
/ metabolism
Alarmins
/ metabolism
Animals
Cell Line, Tumor
DNA-Binding Proteins
/ metabolism
Down-Regulation
/ genetics
Gene Knockout Techniques
Inflammation
/ pathology
Interleukin-2
/ metabolism
Leukocytes
/ metabolism
Mesocricetus
NF-kappa B
/ metabolism
Oncolytic Virotherapy
Oncolytic Viruses
/ metabolism
Pathogen-Associated Molecular Pattern Molecules
/ metabolism
Signal Transduction
Toll-Like Receptor 9
/ metabolism
Transcriptome
/ genetics
Tumor Microenvironment
Tumor Necrosis Factor-alpha
/ metabolism
AIM2
DAMP
PAMP
TILT-123
aenovirus
immunological cell death
immunotherapy
oncolytic virus
virotherapy
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
26 03 2020
26 03 2020
Historique:
received:
28
02
2020
revised:
23
03
2020
accepted:
24
03
2020
entrez:
1
4
2020
pubmed:
1
4
2020
medline:
26
2
2021
Statut:
epublish
Résumé
In order to break tumor resistance towards traditional treatments, we investigate the response of tumor and immune cells to a novel, cytokine-armed oncolytic adenovirus: Ad5/3-d24-E2F-hTNFa-IRES-hIL2 (also known as TILT-123 and OAd.TNFa-IL2). There are several pattern recognition receptors (PRR) that might mediate adenovirus-infection recognition. However, the role and specific effects of each PRR on the tumor microenvironment and treatment outcome remain unclear. Hence, the aim of this study was to investigate the effects of OAd.TNFa-IL2 infection on PRR-mediated danger- and pathogen-associated molecular pattern (DAMP and PAMP, respectively) signaling. In addition, we wanted to see which PRRs mediate an antitumor response and are therefore relevant for optimizing this virotherapy. We determined that OAd.TNFa-IL2 induced DAMP and PAMP release and consequent tumor microenvironment modulation. We show that the AIM2 inflammasome is activated during OAd.TNFa-IL2 virotherapy, thus creating an immunostimulatory antitumor microenvironment.
Identifiants
pubmed: 32225009
pii: cells9040798
doi: 10.3390/cells9040798
pmc: PMC7225950
pii:
doi:
Substances chimiques
Alarmins
0
DNA-Binding Proteins
0
Interleukin-2
0
NF-kappa B
0
Pathogen-Associated Molecular Pattern Molecules
0
Toll-Like Receptor 9
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Références
Front Immunol. 2015 Aug 18;6:422
pubmed: 26347745
Elife. 2014 May 19;3:e01949
pubmed: 24842874
J Biol Chem. 2002 Jun 28;277(26):23888-97
pubmed: 11971907
J Cancer. 2019 Aug 27;10(20):4932-4938
pubmed: 31598165
Mol Ther. 2016 Aug;24(8):1435-43
pubmed: 27357626
Mol Cancer. 2013 Apr 05;12:26
pubmed: 23561329
Ann Oncol. 2015 Aug;26(8):1698-704
pubmed: 25995301
Int J Cancer. 2008 Jan 1;122(1):219-29
pubmed: 17764070
Cell Death Dis. 2013 May 16;4:e631
pubmed: 23681226
Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18538-43
pubmed: 16344461
Annu Rev Immunol. 2018 Apr 26;36:411-433
pubmed: 29677473
Onco Targets Ther. 2017 Feb 13;10:811-817
pubmed: 28243117
J Struct Biol. 2017 Dec;200(3):279-282
pubmed: 28813641
J Leukoc Biol. 2013 Jun;93(6):847-63
pubmed: 23475577
J Am Acad Dermatol. 2014 Nov;71(5):1012-5
pubmed: 25437966
J Immunol. 2001 Feb 1;166(3):1611-7
pubmed: 11160202
BMC Cancer. 2016 Aug 02;16:582
pubmed: 27484466
Mol Ther. 2007 Feb;15(2):378-85
pubmed: 17235317
J Clin Oncol. 2015 Sep 1;33(25):2780-8
pubmed: 26014293
Mol Cancer Ther. 2006 Jan;5(1):1-7
pubmed: 16432157
Ann Pharmacother. 2017 Aug;51(8):675-681
pubmed: 28351167
Mol Ther Oncolytics. 2016 Dec 31;4:77-86
pubmed: 28345026
Cancer Immunol Res. 2014 Sep;2(9):823-30
pubmed: 25187272
J Clin Invest. 2012 Aug;122(8):2711-9
pubmed: 22850880
Hum Gene Ther. 2019 Jun;30(6):740-752
pubmed: 30672366
Am Soc Clin Oncol Educ Book. 2019 Jan;39:165-174
pubmed: 31099649
Int J Cancer. 2012 Jun 15;130(12):2892-902
pubmed: 21805477
Nat Med. 2018 May;24(5):541-550
pubmed: 29686425
Eur J Immunol. 2016 Feb;46(2):269-80
pubmed: 26626159
Crit Rev Eukaryot Gene Expr. 2010;20(2):87-103
pubmed: 21133840
Onco Targets Ther. 2018 Apr 11;11:2063-2073
pubmed: 29695914