Decorin-armed oncolytic adenovirus promotes natural killers (NKs) activation and infiltration to enhance NK therapy in CRC model.
Killer Cells, Natural
/ immunology
Animals
Colorectal Neoplasms
/ therapy
Decorin
/ genetics
Adenoviridae
/ genetics
Humans
Oncolytic Virotherapy
/ methods
Oncolytic Viruses
/ genetics
Mice
Cell Line, Tumor
Xenograft Model Antitumor Assays
Tumor Microenvironment
/ immunology
Lymphocyte Activation
Cell Proliferation
Female
Adoptive NK cell therapy
Colorectal cancer
Decorin
Oncolytic adenovirus
Journal
Molecular biomedicine
ISSN: 2662-8651
Titre abrégé: Mol Biomed
Pays: Singapore
ID NLM: 9918283581406676
Informations de publication
Date de publication:
01 Nov 2024
01 Nov 2024
Historique:
received:
25
03
2024
accepted:
19
09
2024
medline:
1
11
2024
pubmed:
1
11
2024
entrez:
1
11
2024
Statut:
epublish
Résumé
Colorectal cancer (CRC) is a prevalent malignant tumor of the gastrointestinal system, with the third and second highest incidence and mortality rates globally in 2020, respectively. Immunotherapy has developed rapidly in recent years. Natural killer (NK) cells have received increasing attention in the field of tumor immunotherapy due to their recognition and killing tumor cells without the limitations of major histocompatibility complexes. However, constraints within the tumor microenvironment that impede the infiltration and proliferation of NK cells result in poor efficacy of NK cell therapy for solid tumors. Oncolytic viral therapy is an immunogenic treatment with the potential to enhance anti-tumour immune responses and promote immune cell infiltration. In this study, we synergistically combine NK cells with an oncolytic adenovirus carrying Decorin (rAd.DCN) for the treatment of colorectal cancer (CRC) in a xenograft mouse model. By using Flow cytometry, real-time quantitative PCR and Calcein-AM release assay, we found that rAd.DCN could effectively promote proliferation, activation and degranulation of NK cells, up-regulate expression and secretion of NK cell killing activity-related factors, and enhance their killing activity. The efficacy is better than that of the blank control oncolytic virus rAd.Null. Combined treatment significantly inhibited tumor growth, increased the number of NK cells in peripheral blood, promoted the killing function of NK cells, and increased the expression levels of perforin and IFN-γ. At the same time, more NK cells were recruited to infiltrate tumor tissue. Our study established the feasibility of combination NK cells and oncolytic adenovirus application, thus expanding the scope of potentially curative treatments for NK cells in CRC.
Identifiants
pubmed: 39482550
doi: 10.1186/s43556-024-00212-z
pii: 10.1186/s43556-024-00212-z
doi:
Substances chimiques
Decorin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
48Informations de copyright
© 2024. The Author(s).
Références
Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin. 2023;73(3):233–54. https://doi.org/10.3322/caac.21772 .
doi: 10.3322/caac.21772
pubmed: 36856579
Zhang H, Liu X, Zhang W, Deng J, Lin C, Qi Z, et al. Oncogene SCARNA12 as a potential diagnostic biomarker for colorectal cancer. Mol Biomed. 2023;4(1):37. https://doi.org/10.1186/s43556-023-00147-x .
doi: 10.1186/s43556-023-00147-x
pubmed: 37907779
Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet. 2019;394(10207):1467–80. https://doi.org/10.1016/S0140-6736(19)32319-0 .
doi: 10.1016/S0140-6736(19)32319-0
pubmed: 31631858
Cha JH, Chan LC, Song MS, Hung MC. New approaches on cancer immunotherapy. Cold Spring Harb Perspect Med. 2020;10(8):a036863. https://doi.org/10.1101/cshperspect.a036863 .
doi: 10.1101/cshperspect.a036863
pmcid: 7156317
pubmed: 31615865
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252–64. https://doi.org/10.1038/nrc3239 .
doi: 10.1038/nrc3239
pmcid: 4856023
pubmed: 22437870
Rosenberg SA. IL-2: the first effective immunotherapy for human cancer. J Immunol. 2014;192(12):5451–8. https://doi.org/10.4049/jimmunol.1490019 .
doi: 10.4049/jimmunol.1490019
pubmed: 24907378
Peng M, Mo Y, Wang Y, Wu P, Zhang Y, Xiong F, et al. Neoantigen vaccine: an emerging tumor immunotherapy. Mol Cancer. 2019;18(1):128. https://doi.org/10.1186/s12943-019-1055-6 .
doi: 10.1186/s12943-019-1055-6
pmcid: 6708248
pubmed: 31443694
Twumasi-Boateng K, Pettigrew JL, Kwok YYE, Bell JC, Nelson BH. Oncolytic viruses as engineering platforms for combination immunotherapy. Nat Rev Cancer. 2018;18(7):419–32. https://doi.org/10.1038/s41568-018-0009-4 .
doi: 10.1038/s41568-018-0009-4
pubmed: 29695749
Topp MS, Gökbuget N, Stein AS, Zugmaier G, O’Brien S, Bargou RC, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015;16(1):57–66. https://doi.org/10.1016/S1470-2045(14)71170-2 .
doi: 10.1016/S1470-2045(14)71170-2
pubmed: 25524800
Lin M, Luo H, Liang S, Chen J, Liu A, Niu L, et al. Pembrolizumab plus allogeneic NK cells in advanced non-small cell lung cancer patients. J Clin Invest. 2020;130(5):2560–9. https://doi.org/10.1172/JCI132712 .
doi: 10.1172/JCI132712
pubmed: 32027620
Hammer Q, Rückert T, Romagnani C. Natural killer cell specificity for viral infections. Nat Immunol. 2018;19(8):800–8. https://doi.org/10.1038/s41590-018-0163-6 .
doi: 10.1038/s41590-018-0163-6
pubmed: 30026479
Shimasaki N, Jain A, Campana D. NK cells for cancer immunotherapy. Nat Rev Drug Discov. 2020;19(3):200–18. https://doi.org/10.1038/s41573-019-0052-1 .
doi: 10.1038/s41573-019-0052-1
pubmed: 31907401
Kaufman HL, Kohlhapp FJ, Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov. 2015;14(9):642–62. https://doi.org/10.1038/nrd4663 .
doi: 10.1038/nrd4663
pubmed: 26323545
Li QX, Liu G, Wong-Staal F. Oncolytic virotherapy as a personalized cancer vaccine. Int J Cancer. 2008;123(3):493–9. https://doi.org/10.1002/ijc.23692 .
doi: 10.1002/ijc.23692
pubmed: 18500742
Gubbiotti MA, Vallet SD, Ricard-Blum S, Iozzo RV. Decorin interacting network: a comprehensive analysis of decorin-binding partners and their versatile functions. Matrix Biol. 2016;55:7–21. https://doi.org/10.1016/j.matbio.2016.09.009 .
doi: 10.1016/j.matbio.2016.09.009
pubmed: 27693454
Zhao H, Wang H, Kong F, Xu W, Wang T, Xiao F, et al. Oncolytic adenovirus rAd.DCN inhibits breast tumor growth and lung metastasis in an immune-competent orthotopic xenograft model. Hum Gene Ther. 2019;30(2):197–210. https://doi.org/10.1089/hum.2018.055 .
doi: 10.1089/hum.2018.055
pubmed: 30032645
Yang Y, Xu W, Neill T, Hu Z, Wang CH, Xiao X, et al. Systemic delivery of an oncolytic adenovirus expressing decorin for the treatment of breast cancer bone metastases. Hum Gene Ther. 2015;26(12):813–25. https://doi.org/10.1089/hum.2015.098 .
doi: 10.1089/hum.2015.098
pubmed: 26467629
Xu W, Neill T, Yang Y, Hu Z, Cleveland E, Wu Y, et al. The systemic delivery of an oncolytic adenovirus expressing decorin inhibits bone metastasis in a mouse model of human prostate cancer. Gene Ther. 2015;22(3):247–56. https://doi.org/10.1038/gt.2014.110 .
doi: 10.1038/gt.2014.110
pubmed: 25503693
Li F, Sheng Y, Hou W, Sampath P, Byrd D, Thorne S, et al. CCL5-armed oncolytic virus augments CCR5-engineered NK cell infiltration and antitumor efficiency. J Immunother Cancer. 2020;8(1):e000131. https://doi.org/10.1136/jitc-2019-000131 .
doi: 10.1136/jitc-2019-000131
pubmed: 32098828
Ma R, Lu T, Li Z, Teng KY, Mansour AG, Yu M, et al. An Oncolytic virus expressing IL15/IL15Rα combined with off-the-shelf EGFR-CAR NK Cells targets glioblastoma. Cancer Res. 2021;81(13):3635–48. https://doi.org/10.1158/0008-5472.CAN-21-0035 .
doi: 10.1158/0008-5472.CAN-21-0035
pmcid: 8562586
pubmed: 34006525
Chen A, Zhang Y, Meng G, Jiang D, Zhang H, Zheng M, et al. Oncolytic measles virus enhances antitumour responses of adoptive CD8+NKG2D+ cells in hepatocellular carcinoma treatment. Sci Rep. 2017;7:5170. https://doi.org/10.1038/s41598-017-05500-z .
doi: 10.1038/s41598-017-05500-z
pmcid: 5507973
pubmed: 28701757
Jia H, Yang H, Xiong H, Luo KQ. NK cell exhaustion in the tumor microenvironment. Front Immunol. 2023;14:1303605. https://doi.org/10.3389/fimmu.2023.1303605 .
doi: 10.3389/fimmu.2023.1303605
pmcid: 10653587
pubmed: 38022646
Ghasemi M, Abbasi L, GhanbariNaeini L, Kokabian P, NamehGoshayFard N, Givtaj N. Dendritic cells and natural killer cells: the road to a successful oncolytic virotherapy. Front Immunol. 2023;13:950079. https://doi.org/10.3389/fimmu.2022.950079 .
doi: 10.3389/fimmu.2022.950079
pmcid: 9871831
pubmed: 36703982
Cheng M, Chen Y, Xiao W, Sun R, Tian Z. NK cell-bas2ed immunotherapy for malignant diseases. Cell Mol Immunol. 2013;10(3):230–52. https://doi.org/10.1038/cmi.2013.10 .
doi: 10.1038/cmi.2013.10
pmcid: 4076738
pubmed: 23604045
Xiao TS. Innate immunity and inflammation. Cell Mol Immunol. 2017;14(1):1–3. https://doi.org/10.1038/cmi.2016.45 .
doi: 10.1038/cmi.2016.45
pubmed: 27545072
Guo F, Zhang Y, Bai L, Cui J. Natural killer cell therapy targeting cancer stem cells: old wine in a new bottle. Cancer Lett. 2023;570:216328. https://doi.org/10.1016/j.canlet.2023.216328 .
doi: 10.1016/j.canlet.2023.216328
pubmed: 37499742
Walcheck B, Wu J. iNK-CD64/16A cells: a promising approach for ADCC? Expert Opin Biol Ther. 2019;19(12):1229–32. https://doi.org/10.1080/14712598.2019.1667974 .
doi: 10.1080/14712598.2019.1667974
pmcid: 6832865
pubmed: 31510805
Du R, Zhang X, Lu X, Ma X, Guo XY, Shi C, et al. PDPN positive CAFs contribute to HER2 positive breast cancer resistance to trastuzumab by inhibiting antibody-dependent NK cell-mediated cytotoxicity. Drug Resist Updat. 2023;68:100947. https://doi.org/10.1016/j.drup.2023.100947 .
doi: 10.1016/j.drup.2023.100947
pubmed: 36812747
Hodgins JJ, Khan ST, Park MM, Auer RC, Ardolino M. Killers 2.0: NK cell therapies at the forefront of cancer control. J Clin Invest. 2019;129(9):3499–510. https://doi.org/10.1172/JCI129338 .
doi: 10.1172/JCI129338
pmcid: 6715409
pubmed: 31478911
Wu SY, Fu T, Jiang YZ, Shao ZM. Natural killer cells in cancer biology and therapy. Mol Cancer. 2020;19(1):120. https://doi.org/10.1186/s12943-020-01238-x .
doi: 10.1186/s12943-020-01238-x
pubmed: 32762681
Myers JA, Miller JS. Exploring the NK cell platform for cancer immunotherapy. Nat Rev Clin Oncol. 2021;18(2):85–100. https://doi.org/10.1038/s41571-020-0426-7 .
doi: 10.1038/s41571-020-0426-7
pubmed: 32934330
Iozzo RV, Schaefer L. Proteoglycan form and function: a comprehensive nomenclature of proteoglycans. Matrix Biol. 2015;42:11–55. https://doi.org/10.1016/j.matbio.2015.02.003 .
doi: 10.1016/j.matbio.2015.02.003
pubmed: 25701227
Neill T, Painter H, Buraschi S, Owens RT, Lisanti MP, Schaefer L, et al. Decorin antagonizes the angiogenic network: concurrent inhibition of Met, hypoxia inducible factor 1α, vascular endothelial growth factor A, and induction of thrombospondin-1 and TIMP3. J Biol Chem. 2012;287(8):5492–506. https://doi.org/10.1074/jbc.M111.283499 .
doi: 10.1074/jbc.M111.283499
pubmed: 22194599
Buraschi S, Neill T, Owens RT, Iniguez LA, Purkins G, Vadigepalli R, et al. Decorin protein core affects the global gene expression profile of the tumor microenvironment in a triple-negative orthotopic breast carcinoma xenograft model. PLoS One. 2012;7(9):e45559. https://doi.org/10.1371/journal.pone.0045559 .
doi: 10.1371/journal.pone.0045559
pubmed: 23029096
Neill T, Schaefer L, Iozzo RV. Oncosuppressive functions of decorin. Mol Cell Oncol. 2015;2(3):e975645. https://doi.org/10.4161/23723556.2014.975645 .
doi: 10.4161/23723556.2014.975645
pubmed: 27308453
Achard C, Surendran A, Wedge ME, Ungerechts G, Bell J, Ilkow CS. Lighting a fire in the tumor microenvironment using oncolytic immunotherapy. EBioMedicine. 2018;31:17–24. https://doi.org/10.1016/j.ebiom.2018.04.020 .
doi: 10.1016/j.ebiom.2018.04.020
pubmed: 29724655
McGrath K, Dotti G. Combining oncolytic viruses with chimeric antigen receptor T cell therapy. Hum Gene Ther. 2021;32(3–4):150–7. https://doi.org/10.1089/hum.2020.278 .
doi: 10.1089/hum.2020.278
pubmed: 33349123
Watanabe N, McKenna MK, Rosewell Shaw A, Suzuki M. Clinical CAR-T cell and oncolytic virotherapy for cancer treatment. Mol Ther. 2021;29(2):505–20. https://doi.org/10.1016/j.ymthe.2020.10.023 .
doi: 10.1016/j.ymthe.2020.10.023
pubmed: 33130314
Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008;9(5):503–10. https://doi.org/10.1038/ni1582 .
doi: 10.1038/ni1582
pubmed: 18425107
Leung EYL, Ennis DP, Kennedy PR, Hansell C, Dowson S, Farquharson M, et al. NK Cells augment oncolytic adenovirus cytotoxicity in ovarian cancer. Mol Ther Oncolytics. 2020;16:289–301. https://doi.org/10.1016/j.omto.2020.02.001 .
doi: 10.1016/j.omto.2020.02.001
pmcid: 7068056
pubmed: 32195317
Mahasa KJ, Eaddadi A, de Pillis L, Ouifki R. Oncolytic potency and reduced virus tumor-specificity in oncolytic virotherapy. A mathematical modelling approach. PLoS One. 2017;12(9):e0184347. https://doi.org/10.1371/journal.pone.0184347 .
doi: 10.1371/journal.pone.0184347
pmcid: 5608221
pubmed: 28934210
Lemos de Matos A, Franco LS, McFadden G. Oncolytic viruses and the immune system: the dynamic duo. Mol Ther Methods Clin Dev. 2020;17:349–58. https://doi.org/10.1016/j.omtm.2020.01.001 .
doi: 10.1016/j.omtm.2020.01.001
pmcid: 7015832
pubmed: 32071927
Alvarez-Breckenridge CA, Yu J, Price R, Wojton J, Pradarelli J, Mao H, et al. NK cells impede glioblastoma virotherapy through NKp30 and NKp46 natural cytotoxicity receptors. Nat Med. 2012;18(12):1827–34. https://doi.org/10.1038/nm.3013 .
doi: 10.1038/nm.3013
pmcid: 3668784
pubmed: 23178246
Hu ZB, Wu CT, Wang H, Zhang QW, Wang L, Wang RL, et al. A simplified system for generating oncolytic adenovirus vector carrying one or two transgenes. Cancer Gene Ther. 2008;15(3):173–82. https://doi.org/10.1038/sj.cgt.7701105 .
doi: 10.1038/sj.cgt.7701105
pubmed: 18157145
Metelitsa LS, Naidenko OV, Kant A, Wu HW, Loza MJ, Perussia B, et al. Human NKT cells mediate antitumor cytotoxicity directly by recognizing target cell CD1d with bound ligand or indirectly by producing IL-2 to activate NK cells. J Immunol. 2001;167(6):3114–22. https://doi.org/10.4049/jimmunol.167.6.3114 .
doi: 10.4049/jimmunol.167.6.3114
pubmed: 11544296