Impact of tumor microenvironment on oncolytic viral therapy.
Interactions between tumor cells and their microenvironment have been shown to play a very significant role in the initiation, progression, and invasiveness of cancer. These tumor-stromal interactions are capable of altering the delivery and effectiveness of therapeutics into the tumor and are also known to influence future resistance and re-growth after treatment. Here we review recent advances in the understanding of the tumor microenvironment and its response to oncolytic viral therapy. The multifaceted environmental response to viral therapy can influence viral infection, replication, and propagation within the tumor. Recent studies have unveiled the complicated temporal changes in the tumor vasculature post-oncolytic virus (OV) treatment, and their impact on tumor biology. Similarly, the secreted extracellular matrix in solid tumors can affect both infection and spread of the therapeutic virus. Together, these complex changes in the tumor microenvironment also modulate the activation of the innate antiviral host immune response, leading to quick and efficient viral clearance. In order to combat these detrimental responses, viruses have been combined with pharmacological adjuvants and "armed" with therapeutic genes in order to suppress the pernicious environmental conditions following therapy. In this review we will discuss the impact of the tumor environment on viral therapy and examine some of the recent literature investigating methods of modulating this environment to enhance oncolysis.
Wojton
Jeffrey
J
Dardinger Laboratory for Neuro-oncology and Neurosciences, Department of Neurological Surgery, James Comprehensive Cancer Center, Columbus, OH 43210, United States.
Kaur
Balveen
B
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000276:immunology / Q000502:physiology*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab
Mol Ther. 2007 Nov;15(11):1982-90
17653103
Nat Clin Pract Oncol. 2007 Feb;4(2):101-17
17259931
Gene Ther. 2005 Jun;12(11):911-7
15690061
J Immunol. 2008 May 1;180(9):6018-26
18424722
J Virol. 2000 May;74(10):4765-75
10775615
Mol Ther. 2008 Jun;16(6):1041-7
18388912
Anticancer Agents Med Chem. 2006 Sep;6(5):407-28
17017851
Hum Gene Ther. 2000 Nov 1;11(16):2219-30
11084679
Cell Cycle. 2009 Jul 15;8(14):2194-7
19502787
J Immunol. 2009 Feb 1;182(3):1763-9
19155526
Mol Ther. 2001 May;3(5 Pt 1):697-707
11356075
Circ Res. 2005 Jan 7;96(1):15-26
15637304
Clin Cancer Res. 2008 Jun 15;14(12):3933-41
18559615
J Virol. 2004 Sep;78(17):8960-70
15308693
J Virol. 2005 Aug;79(16):10589-600
16051851
Cancer Res. 2007 Oct 1;67(19):9398-406
17909049
Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):14981-6
18815361
J Virol. 2001 Oct;75(20):9828-35
11559816
Chem Rev. 2009 Jul;109(7):3125-40
19462957
Mol Ther. 2008 Jan;16(1):146-53
18071337
Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5247-51
8202476
J Gen Virol. 2008 Jan;89(Pt 1):1-47
18089727
Hum Gene Ther. 2005 Jun;16(6):765-78
15960607
Cancer Chemother Pharmacol. 2009 Nov;64(6):1201-10
19308409
Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9578-83
15210966
Proc Natl Acad Sci U S A. 1998 May 26;95(11):6355-60
9600969
J Virol. 2010 Jan;84(2):856-66
19906926
Neoplasia. 2004 Nov-Dec;6(6):725-35
15720798
Mol Ther. 2005 Nov;12(5):789-802
15925544
Mol Ther. 2010 Feb;18(2):285-94
19844198
Mol Ther. 2004 Nov;10(5):938-49
15509511
J Natl Cancer Inst. 2006 Oct 18;98(20):1482-93
17047197
Gene Ther. 2010 Feb;17(2):190-201
19907500
Cancer Biol Ther. 2006 Jan;5(1):48-53
16294031
Gene Ther. 2009 Aug;16(8):1009-20
19440223
Cancer Res. 2007 Jan 15;67(2):440-4
17234749
Mol Cancer Ther. 2007 Oct;6(10):2728-36
17938266
Mol Ther. 2007 Mar;15(3):588-97
17245355
Clin Cancer Res. 2009 Apr 15;15(8):2777-88
19351762
Clin Cancer Res. 2008 Oct 15;14(20):6505-14
18927290
Recent Pat CNS Drug Discov. 2009 Jan;4(1):1-13
19149710
Hum Gene Ther. 2003 Mar 20;14(5):425-33
12691608
Glia. 2003 Apr 1;42(1):77-88
12594739
Cancer Res. 2006 Mar 1;66(5):2509-13
16510565
Gene Ther. 2006 Jun;13(12):986-90
16525485
J Clin Invest. 2002 Oct;110(8):1105-11
12393846
Clin Cancer Res. 2009 Jan 15;15(2):561-9
19147761
Mol Ther. 2008 Aug;16(8):1382-91
18545226
Curr Gene Ther. 2009 Oct;9(5):341-55
19860649
Mol Ther. 2007 Sep;15(9):1686-93
17579581
Mol Ther. 2008 Oct;16(10):1665-73
18665155
Curr Mol Med. 2003 Nov;3(7):643-51
14601638
Nat Med. 2004 Feb;10(2):145-7
14745444
Mol Ther. 2009 Jan;17(1):199-207
18957964
Gene Ther. 2010 Feb;17(2):202-16
19829315
Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12915-20
19617539
Mol Cancer Res. 2007 Jul;5(7):655-65
17634421
J Natl Cancer Inst. 2007 Dec 5;99(23):1768-81
18042934
Curr Cancer Drug Targets. 2007 Mar;7(2):181-9
17346110
Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12873-8
16908838
Science. 2008 Apr 4;320(5872):38-41
18388269
Mol Ther. 2008 May;16(5):879-85
18388918
Annu Rev Immunol. 2001;19:65-91
11244031
Nat Rev Cancer. 2003 Jun;3(6):401-10
12778130
Mol Ther. 2007 Feb;15(2):279-86
17235305
Mol Ther. 2009 Jan;17(1):51-6
18957963
Nature. 2000 Sep 14;407(6801):249-57
11001068
Leukemia. 2017 Dec;31(12):2791-2798
28439108
Mol Ther. 2008 Sep;16(9):1546-55
18648350
Cancer Res. 2000 May 1;60(9):2497-503
10811131
Gene Ther. 2005 Jun;12(11):902-10
15690062