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Cancer Cell International
Published in: Cancer Cell International 1/2022

Open Access 01-12-2022 | Adenovirus | Review

Modifying oncolytic virotherapy to overcome the barrier of the hypoxic tumor microenvironment. Where do we stand?

Authors: Sara Shayan, Arash Arashkia, Kayhan Azadmanesh

Published in: Cancer Cell International | Issue 1/2022

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Abstract

Viruses are completely dependent on host cell machinery for their reproduction. As a result, factors that influence the state of cells, such as signaling pathways and gene expression, could determine the outcome of viral pathogenicity. One of the important factors influencing cells or the outcome of viral infection is the level of oxygen. Recently, oncolytic virotherapy has attracted attention as a promising approach to improving cancer treatment. However, it was shown that tumor cells are mostly less oxygenated compared with their normal counterparts, which might affect the outcome of oncolytic virotherapy. Therefore, knowing how oncolytic viruses could cope with stressful environments, particularly hypoxic environments, might be essential for improving oncolytic virotherapy.
Literature
1.
2.
Rocha S. Gene regulation under low oxygen: holding your breath for transcription. Trends Biochem Sci. 2007;32(8):389–97.PubMed
3.
Haghighi-Najafabadi N, Roohvand F, Shams Nosrati MS, Teimoori-Toolabi L, Azadmanesh K. Oncolytic herpes simplex virus type-1 expressing IL-12 efficiently replicates and kills human colorectal cancer cells. Microb Pathog. 2021;160: 105164.PubMed
4.
Abdoli S, Roohvand F, Teimoori-Toolabi L, Shokrgozar MA, Bahrololoumi M, Azadmanesh K. Construction of various γ345 deleted fluorescent-expressing oncolytic herpes simplex type 1 (oHSV) for generation and isolation of HSV-based vectors. Iran Biomed J. 2017;21(4):206–17.PubMedPubMedCentral
5.
Abdoli S, Roohvand F, Teimoori-Toolabi L, Shayan S, Shokrgozar MA. Cytotoxic effect of dual fluorescent-labeled oncolytic herpes simplex virus type 1 on mouse tumorigenic cell lines. Res Pharm Sci. 2019;14(1):27–35.PubMedPubMedCentral
6.
Tilgase A, Patetko L, Blāķe I, Ramata-Stunda A, Borodušķis M, Alberts P. Effect of the oncolytic ECHO-7 virus Rigvir® on the viability of cell lines of human origin in vitro. J Cancer. 2018;9(6):1033–49.PubMedPubMedCentral
7.
Liang M. Oncorine, the world first oncolytic virus medicine and its update in China. Curr Cancer Drug Targets. 2018;18(2):171–6.PubMed
8.
Conry RM, Westbrook B, McKee S, Norwood TG. Talimogene laherparepvec: first in class oncolytic virotherapy. Hum Vaccin Immunother. 2018;14(4):839–46.PubMedPubMedCentral
9.
Zeng J, Li X, Sander M, Zhang H, Yan G, Lin Y. Oncolytic viro-immunotherapy: an emerging option in the treatment of gliomas. Front Immunol. 2021;12:721830.PubMedPubMedCentral
10.
Guo ZS. The impact of hypoxia on oncolytic virotherapy. Virus Adapt Treat. 2011;3:71–82.
11.
Chun YS, Adusumilli PS, Fong Y. Employing tumor hypoxia for oncolytic therapy in breast cancer. J Mammary Gland Biol Neoplasia. 2005;10(4):311–8.PubMed
12.
Hay JG. The potential impact of hypoxia on the success of oncolytic virotherapy. Curr Opin Mol Ther. 2005;7(4):353–8.PubMed
13.
Hardcastle J, Kurozumi K, Chiocca EA, Kaur B. Oncolytic viruses driven by tumor-specific promoters. Curr Cancer Drug Targets. 2007;7(2):181–9.PubMed
14.
Wong HH, Lemoine NR, Wang Y. Oncolytic viruses for cancer therapy: overcoming the obstacles. Viruses. 2010;2(1):78–106.PubMedPubMedCentral
15.
Wojton J, Kaur B. Impact of tumor microenvironment on oncolytic viral therapy. Cytokine Growth Factor Rev. 2010;21(2–3):127–34.PubMedPubMedCentral
16.
Fukuhara H, Ino Y, Todo T. Oncolytic virus therapy: a new era of cancer treatment at dawn. Cancer Sci. 2016;107(10):1373–9.PubMedPubMedCentral
17.
Achard C, Surendran A, Wedge M-E, Ungerechts G, Bell J, Ilkow CS. Lighting a fire in the tumor microenvironment using oncolytic immunotherapy. EBioMedicine. 2018;31:17–24.PubMedPubMedCentral
18.
Hadryś A, Sochanik A, McFadden G, Jazowiecka-Rakus J. Mesenchymal stem cells as carriers for systemic delivery of oncolytic viruses. Eur J Pharmacol. 2020;874:172991.PubMed
19.
Wang L, Chard Dunmall LS, Cheng Z, Wang Y. Remodeling the tumor microenvironment by oncolytic viruses: beyond oncolysis of tumor cells for cancer treatment. J Immunother Cancer. 2022;10(5):e004167.PubMedPubMedCentral
20.
Baghban R, Roshangar L, Jahanban-Esfahlan R, Seidi K, Ebrahimi-Kalan A, Jaymand M, et al. Tumor microenvironment complexity and therapeutic implications at a glance. Cell Commun Signal. 2020;18(1):59.PubMedPubMedCentral
21.
Tsai M-J, Chang W-A, Huang M-S, Kuo P-L. Tumor microenvironment: a new treatment target for cancer. ISRN Biochem. 2014;2014:351959.PubMedPubMedCentral
22.
Senthebane DA, Rowe A, Thomford NE, Shipanga H, Munro D, Mazeedi MAMA, et al. The role of tumor microenvironment in chemoresistance: to survive, keep your enemies closer. Int J Mol Sci. 2017;18(7):1586.PubMedPubMedCentral
23.
Garnier L, Gkountidi A-O, Hugues S. Tumor-associated lymphatic vessel features and immunomodulatory functions. Front Immunol. 2019;10:720.PubMedPubMedCentral
24.
Pierson DJ. Pathophysiology and clinical effects of chronic hypoxia. Respir Care. 2000;45(1):39–51.PubMed
25.
Saxena K, Jolly MK. Acute vs. chronic vs. cyclic hypoxia: their differential dynamics, molecular mechanisms, and effects on tumor progression. Biomolecules. 2019;9(8):339.PubMedPubMedCentral
26.
Mehrabi M, Amini F, Mehrabi S. Active role of the necrotic zone in desensitization of hypoxic macrophages and regulation of CSC-fate: a hypothesis. Front Oncol. 2018;8:235.PubMedPubMedCentral
27.
Sebestyén A, Kopper L, Dankó T, Tímár J. Hypoxia signaling in cancer: from basics to clinical practice. Pathol Oncol Res. 2021;27:1609802.PubMedPubMedCentral
28.
Jing X, Yang F, Shao C, Wei K, Xie M, Shen H, et al. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer. 2019;18(1):157.PubMedPubMedCentral
29.
Walsh JC, Lebedev A, Aten E, Madsen K, Marciano L, Kolb HC. The clinical importance of assessing tumor hypoxia: relationship of tumor hypoxia to prognosis and therapeutic opportunities. Antioxid Redox Signal. 2014;21(10):1516–54.PubMedPubMedCentral
30.
Shi R, Liao C, Zhang Q. Hypoxia-driven effects in cancer: characterization, mechanisms, and therapeutic implications. Cells. 2021;10(3):678.PubMedPubMedCentral
31.
Tanabe S, Quader S, Cabral H, Ono R. Interplay of EMT and CSC in cancer and the potential therapeutic strategies. Front Pharmacol. 2020;11:904.PubMedPubMedCentral
32.
33.
Muz B, de la Puente P, Azab F, Azab AK. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia. 2015;3:83–92.PubMedPubMedCentral
34.
35.
Oh CM, Chon HJ, Kim C. Combination immunotherapy using oncolytic virus for the treatment of advanced solid tumors. Int J Mol Sci. 2020;21:20.
36.
Ferguson MS, Lemoine NR, Wang Y. Systemic delivery of oncolytic viruses: hopes and hurdles. Adv Virol. 2012;2012:805629.PubMedPubMedCentral
37.
Xie R, Bi X, Shang B, Zhou A, Shi H, Shou J. Efficacy and safety of oncolytic viruses in advanced or metastatic cancer: a network meta-analysis. Virol J. 2021;18(1):158.PubMedPubMedCentral
38.
Ma S, Zhao Y, Lee WC, Ong L-T, Lee PL, Jiang Z, et al. Hypoxia induces HIF1α-dependent epigenetic vulnerability in triple negative breast cancer to confer immune effector dysfunction and resistance to anti-PD-1 immunotherapy. Nat Commun. 2022;13(1):4118.PubMedPubMedCentral
39.
40.
Liu Y, Cox SR, Morita T, Kourembanas S. Hypoxia regulates vascular endothelial growth factor gene expression in endothelial cells. Identification of a 5’ enhancer. Circ Res. 1995;77(3):638–43.PubMed
41.
Rhim JH, Tosato G. Targeting the tumor vasculature to improve the efficacy of oncolytic virus therapy. JNCI J Nat Cancer Inst. 2007;99(23):1739–41.PubMed
42.
Hou W, Chen H, Rojas J, Sampath P, Thorne SH. Oncolytic vaccinia virus demonstrates antiangiogenic effects mediated by targeting of VEGF. Int J Cancer. 2014;135(5):1238–46.PubMedPubMedCentral
43.
Carew JS, Espitia CM, Zhao W, Mita MM, Mita AC, Nawrocki ST. Oncolytic reovirus inhibits angiogenesis through induction of CXCL10/IP-10 and abrogation of HIF activity in soft tissue sarcomas. Oncotarget. 2017;8(49):86769–83.PubMedPubMedCentral
44.
Hwang II, Watson IR, Der SD, Ohh M. Loss of VHL confers hypoxia-inducible factor (HIF)-dependent resistance to vesicular stomatitis virus: role of HIF in antiviral response. J Virol. 2006;80(21):10712–23.PubMedPubMedCentral
45.
Hassanzadeh A, Altajer AH, Rahman HS, Saleh MM, Bokov DO, Abdelbasset WK, et al. Mesenchymal stem/stromal cell-based delivery: a rapidly evolving strategy for cancer therapy. Front Cell Dev Biol. 2021;9:686453.PubMedPubMedCentral
46.
Koks CA, De Vleeschouwer S, Graf N, Van Gool SW. Immune suppression during oncolytic virotherapy for high-grade glioma; yes or no? J Cancer. 2015;6(3):203–17.PubMedPubMedCentral
47.
Hai C, Jin YM, Jin WB, Han ZZ, Cui MN, Piao XZ, et al. Application of mesenchymal stem cells as a vehicle to deliver replication-competent adenovirus for treating malignant glioma. Chin J Cancer. 2012;31(5):233–40.PubMedPubMedCentral
48.
Yousaf I, Kaeppler J, Frost S, Seymour LW, Jacobus EJ. Attenuation of the hypoxia inducible factor pathway after oncolytic adenovirus infection coincides with decreased vessel perfusion. Cancers. 2020;12:4.
49.
Zhang W, Zhang C, Tian W, Qin J, Chen J, Zhang Q, et al. Efficacy of an oncolytic adenovirus driven by a chimeric promoter and armed with decorin against renal cell carcinoma. Hum Gene Ther. 2020;31(11–12):651–63.PubMed
50.
Kurozumi K, Hardcastle J, Thakur R, Yang M, Christoforidis G, Fulci G, et al. Effect of tumor microenvironment modulation on the efficacy of oncolytic virus therapy. J Natl Cancer Inst. 2007;99(23):1768–81.PubMed
51.
Matuszewska K, Santry LA, van Vloten JP, AuYeung AWK, Major PP, Lawler J, et al. Combining vascular normalization with an oncolytic virus enhances immunotherapy in a preclinical model of advanced-stage ovarian cancer. Clin Cancer Res. 2019;25(5):1624–38.PubMed
52.
Wang B, Zhao Q, Zhang Y, Liu Z, Zheng Z, Liu S, et al. Targeting hypoxia in the tumor microenvironment: a potential strategy to improve cancer immunotherapy. J Exp Clin Cancer Res. 2021;40(1):24.PubMedPubMedCentral
53.
54.
Sethumadhavan S, Silva M, Philbrook P, Nguyen T, Hatfield SM, Ohta A, et al. Hypoxia and hypoxia-inducible factor (HIF) downregulate antigen-presenting MHC class I molecules limiting tumor cell recognition by T cells. PLoS ONE. 2017;12(11):e0187314.PubMedPubMedCentral
55.
Kurokawa C, Galanis E. Interferon signaling predicts response to oncolytic virotherapy. Oncotarget. 2019;10(16):1544–5.PubMedPubMedCentral
56.
Sevenich L. Turning, “cold” into “hot” tumors—opportunities and challenges for radio-immunotherapy against primary and metastatic brain cancers. Front Oncol. 2019;163:3.
57.
Jun JC, Rathore A, Younas H, Gilkes D, Polotsky VY. Hypoxia-inducible factors and cancer. Curr Sleep Med Rep. 2017;3(1):1–10.PubMedPubMedCentral
58.
Bargou R, Leo E, Zugmaier G, Klinger M, Goebeler M, Knop S, et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science. 2008;321(5891):974–7.PubMed
59.
60.
Yamada S, Utsunomiya T, Morine Y, Imura S, Ikemoto T, Arakawa Y, et al. Expressions of hypoxia-inducible factor-1 and epithelial cell adhesion molecule are linked with aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation therapy. Ann Surg Oncol. 2014;21(Suppl 3):S436–42.PubMed
61.
Freedman JD, Hagel J, Scott EM, Psallidas I, Gupta A, Spiers L, et al. Oncolytic adenovirus expressing bispecific antibody targets T-cell cytotoxicity in cancer biopsies. EMBO Mol Med. 2017;9(8):1067–87.PubMedPubMedCentral
62.
Yahyazadeh Mashhadi SM, Kazemimanesh M, Arashkia A, Azadmanesh K, Meshkat Z, Golichenari B, et al. Shedding light on the EpCAM: an overview. J Cell Physiol. 2019;234(8):12569–80.PubMed
63.
Ilkow CS, Marguerie M, Batenchuk C, Mayer J, Ben Neriah D, Cousineau S, et al. Reciprocal cellular cross-talk within the tumor microenvironment promotes oncolytic virus activity. Nat Med. 2015;21(5):530–6.PubMed
64.
Yu F, Wang X, Guo ZS, Bartlett DL, Gottschalk SM, Song XT. T-cell engager-armed oncolytic vaccinia virus significantly enhances antitumor therapy. Mol Ther. 2014;22(1):102–11.PubMed
65.
Majzner RG, Mackall CL. Tumor antigen escape from CAR T-cell therapy. Cancer Discov. 2018;8(10):1219–26.PubMed
66.
Wing A, Fajardo CA, Posey AD Jr, Shaw C, Da T, Young RM, et al. Improving CART-cell therapy of solid tumors with oncolytic virus-driven production of a bispecific T-cell engager. Cancer Immunol Res. 2018;6(5):605–16.PubMedPubMedCentral
67.
Liu B, Qian S-B. Translational reprogramming in cellular stress response. Wiley Interdiscip Rev RNA. 2014;5(3):301–15.PubMed
68.
69.
Aghi MK, Liu TC, Rabkin S, Martuza RL. Hypoxia enhances the replication of oncolytic herpes simplex virus. Mol Ther. 2009;17(1):51–6.PubMed
70.
Reinblatt M, Pin RH, Federoff HJ, Fong Y. Utilizing tumor hypoxia to enhance oncolytic viral therapy in colorectal metastases. Ann Surg. 2004;239(6):892–902.PubMedPubMedCentral
71.
Fasullo M, Burch A, Britton A. Hypoxia enhances the replication of oncolytic herpes simplex virus in p53- breast cancer cells. Cell Cycle. 2009;8(14):2194–7.PubMed
72.
Shayan S, Arashkia A, Bahramali G, Abdoli A, Nosrati MSS, Azadmanesh K. Cell type-specific response of colon cancer tumor cell lines to oncolytic HSV-1 virotherapy in hypoxia. Cancer Cell Int. 2022;22(1):164.PubMedPubMedCentral
73.
74.
75.
Damdinsuren B, Nagano H, Kondo M, Natsag J, Hanada H, Nakamura M, et al. TGF-beta1-induced cell growth arrest and partial differentiation is related to the suppression of Id1 in human hepatoma cells. Oncol Rep. 2006;15(2):401–8.PubMed
76.
Sgubin D, Wakimoto H, Kanai R, Rabkin SD, Martuza RL. Oncolytic herpes simplex virus counteracts the hypoxia-induced modulation of glioblastoma stem-like cells. Stem Cells Transl Med. 2012;1(4):322–32.PubMedPubMedCentral
77.
Friedman GK, Haas MC, Kelly VM, Markert JM, Gillespie GY, Cassady KA. Hypoxia moderates γ(1)34.5-deleted herpes simplex virus oncolytic activity in human glioma xenoline primary cultures. Transl Oncol. 2012;5(3):200–7.PubMedPubMedCentral
78.
Hernandez-Alcoceba R, Pihalja M, Qian D, Clarke MF. New oncolytic adenoviruses with hypoxia—and estrogen receptor-regulated replication. Hum Gene Ther. 2002;13(14):1737–50.PubMed
79.
Post DE, Van Meir EG. A novel hypoxia-inducible factor (HIF) activated oncolytic adenovirus for cancer therapy. Oncogene. 2003;22(14):2065–72.PubMed
80.
Hashimoto Y, Tazawa H, Teraishi F, Kojima T, Watanabe Y, Uno F, et al. The hTERT promoter enhances the antitumor activity of an oncolytic adenovirus under a hypoxic microenvironment. PLoS ONE. 2012;7(6):e39292.PubMedPubMedCentral
81.
Oh E, Hong J, Kwon O-J, Yun C-O. A hypoxia- and telomerase-responsive oncolytic adenovirus expressing secretable trimeric TRAIL triggers tumour-specific apoptosis and promotes viral dispersion in TRAIL-resistant glioblastoma. Sci Rep. 2018;8(1):1420.PubMedPubMedCentral
82.
Kwon O-J, Kim P-H, Huyn S, Wu L, Kim M, Yun C-O. A Hypoxia- and α-fetoprotein–dependent oncolytic adenovirus exhibits specific killing of hepatocellular carcinomas. Clin Cancer Res. 2010;16(24):6071–82.PubMed
83.
Yu F, White SB, Zhao Q, Lee FS. Dynamic, site-specific interaction of hypoxia-inducible factor-1α with the von hippel-lindau tumor suppressor protein. Can Res. 2001;61(10):4136–42.
84.
Krieg M, Haas R, Brauch H, Acker T, Flamme I, Plate KH. Up-regulation of hypoxia-inducible factors HIF-1α and HIF-2α under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function. Oncogene. 2000;19(48):5435–43.PubMed
85.
Ch’ng WC, Stanbridge EJ, Yusoff K, Shafee N. The oncolytic activity of newcastle disease virus in clear cell renal carcinoma cells in normoxic and hypoxic conditions: the interplay between von hippel-lindau and interferon-β signaling. J Interferon Cytokine Res. 2013;33(7):346–54.PubMedPubMedCentral
86.
Hiley CT, Yuan M, Lemoine NR, Wang Y. Lister strain vaccinia virus, a potential therapeutic vector targeting hypoxic tumours. Gene Ther. 2010;17(2):281–7.PubMed
87.
Hastie E, Grdzelishvili VZ. Vesicular stomatitis virus as a flexible platform for oncolytic virotherapy against cancer. J Gen Virol. 2012;93(Pt 12):2529–45.PubMedPubMedCentral
88.
Connor JH, Naczki C, Koumenis C, Lyles DS. Replication and cytopathic effect of oncolytic vesicular stomatitis virus in hypoxic tumor cells in vitro and in vivo. J Virol. 2004;78(17):8960–70.PubMedPubMedCentral
89.
Zhou Y, Wen F, Zhang P, Tang R, Li Q. Vesicular stomatitis virus is a potent agent for the treatment of malignant ascites. Oncol Rep. 2016;35(3):1573–81.PubMed
90.
Carew JS, Espitia CM, Zhao W, Kelly KR, Coffey M, Freeman JW, et al. Reolysin is a novel reovirus-based agent that induces endoplasmic reticular stress-mediated apoptosis in pancreatic cancer. Cell Death Dis. 2013;4(7):e728.PubMedPubMedCentral
91.
Cho IR, Koh SS, Min HJ, Park EH, Ratakorn S, Jhun BH, et al. Down-regulation of HIF-1alpha by oncolytic reovirus infection independently of VHL and p53. Cancer Gene Ther. 2010;17(5):365–72.PubMed
92.
Gupta-Saraf P, Miller CL. HIF-1α downregulation and apoptosis in hypoxic prostate tumor cells infected with oncolytic mammalian orthoreovirus. Oncotarget. 2014;5(2):561–74.PubMedPubMedCentral
93.
Hotani T, Mizuguchi H, Sakurai F. Systemically administered reovirus-induced downregulation of hypoxia inducible factor-1α in subcutaneous tumors. Mol Ther Oncolytics. 2018;12:162–72.PubMedPubMedCentral
94.
Figová K, Hraběta J, Eckschlager T. Anticancer efficiency of reovirus in normoxia and hypoxia. Folia Biol. 2013;59(2):68–75.
Metadata
Title
Modifying oncolytic virotherapy to overcome the barrier of the hypoxic tumor microenvironment. Where do we stand?
Authors
Sara Shayan
Arash Arashkia
Kayhan Azadmanesh
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2022
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-022-02774-w

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