{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T13:29:23Z","timestamp":1773494963239,"version":"3.50.1"},"reference-count":121,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,7,9]],"date-time":"2019-07-09T00:00:00Z","timestamp":1562630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["RSG-15-184-01"],"award-info":[{"award-number":["RSG-15-184-01"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent, but generally asymptomatic, infection in most people in the world. However, CMV drives and sustains extremely large numbers of antigen-specific T cells and is, therefore, emerging as an exciting platform for vaccines against infectious diseases and cancer. Indeed, pre-clinical data strongly suggest that CMV-based vaccines can sustain protective CD8+ T cell and antibody responses. In the context of vaccines for infectious diseases, substantial pre-clinical studies have elucidated the efficacy and protective mechanisms of CMV-based vaccines, including in non-human primate models of various infections. In the context of cancer vaccines, however, much less is known and only very early studies in mice have been conducted. To develop CMV-based cancer vaccines further, it will be critical to better understand the complex interaction of CMV and cancer. An array of evidence suggests that naturally-acquired human (H)CMV can be detected in cancers, and it has been proposed that HCMV may promote tumor growth. This would obviously be a concern for any therapeutic cancer vaccines. In experimental models, CMV has been shown to play both positive and negative roles in tumor progression, depending on the model studied. However, the mechanisms are still largely unknown. Thus, more studies assessing the interaction of CMV with the tumor microenvironment are needed. This review will summarize the existing literature and major open questions about CMV-based vaccines for cancer, and discuss our hypothesis that the balance between pro-tumor and anti-tumor effects driven by CMV depends on the location and the activity of the virus in the lesion.<\/jats:p>","DOI":"10.3390\/vaccines7030062","type":"journal-article","created":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T03:05:26Z","timestamp":1562727926000},"page":"62","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["From Vaccine Vector to Oncomodulation: Understanding the Complex Interplay between CMV and Cancer"],"prefix":"10.3390","volume":"7","author":[{"given":"Nicole A.","family":"Wilski","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher M.","family":"Snyder","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.imlet.2018.01.011","article-title":"Therapeutic cancer vaccines: From initial findings to prospects","volume":"196","author":"Song","year":"2018","journal-title":"Immunol. Lett."},{"key":"ref_2","first-page":"5883","article-title":"Active Specific Immunotherapy for Melanoma: Phase I Trial of Allogeneic Lysates and a Novel Adjuvant","volume":"48","author":"Mitchell","year":"1988","journal-title":"Cancer Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.semcancer.2003.09.004","article-title":"Results of clinical trials with an allogeneic melanoma tumor cell lysate vaccine: Melacine\u00ae","volume":"13","author":"Sondak","year":"2003","journal-title":"Semin. Cancer Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1128\/CMR.00034-08","article-title":"Immunobiology of Human Cytomegalovirus: From Bench to Bedside","volume":"22","author":"Crough","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1128\/CMR.00062-12","article-title":"The \u201csilent\u201d global burden of congenital cytomegalovirus","volume":"26","author":"Manicklal","year":"2013","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/path.4437","article-title":"The pathogenesis of human cytomegalovirus","volume":"235","author":"Griffiths","year":"2015","journal-title":"J. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Reddehase, M.J., and Lemmermann, N.A.W. (2019). Cellular reservoirs of latent cytomegaloviruses. Med. Microbiol. Immunol.","DOI":"10.1007\/s00430-019-00592-y"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.antiviral.2018.09.003","article-title":"New therapies for human cytomegalovirus infections","volume":"159","author":"Britt","year":"2018","journal-title":"Antiviral Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1016\/S0140-6736(05)70487-6","article-title":"Simultaneous infection of healthy people with multiple human cytomegalovirus strains","volume":"352","author":"Ebert","year":"1998","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1056\/NEJM200105033441804","article-title":"Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity","volume":"344","author":"Boppana","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.4049\/jimmunol.170.4.2022","article-title":"Memory inflation: Continuous accumulation of antiviral CD8+ T cells over time","volume":"170","author":"Karrer","year":"2003","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/S0531-5565(03)00134-7","article-title":"Age-associated accumulation of CMV-specific CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1)","volume":"38","author":"Ouyang","year":"2003","journal-title":"Exp. Gerontol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1002\/eji.200425534","article-title":"Evolution of diverse antiviral CD8+ T cell populations after murine cytomegalovirus infection","volume":"35","author":"Sierro","year":"2005","journal-title":"Eur. J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1084\/jem.20050882","article-title":"Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects","volume":"202","author":"Sylwester","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.immuni.2008.07.017","article-title":"Memory Inflation During Chronic Viral Infection is Maintained by Continuous Production of Short-Lived Functional T Cells","volume":"29","author":"Snyder","year":"2008","journal-title":"Immunity"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Smith, C.J., Turula, H., and Snyder, C.M. (2014). Systemic Hematogenous Maintenance of Memory Inflation by MCMV Infection. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004233"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1128\/JVI.76.1.151-164.2002","article-title":"Two antigenic peptides from genes m123 and m164 of murine cytomegalovirus quantitatively dominate CD8 T-cell memory in the H-2d haplotype","volume":"76","author":"Holtappels","year":"2002","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1046\/j.1365-2249.2003.02266.x","article-title":"Population analysis of antiviral T cell responses using MHC class I-peptide tetramers","volume":"134","author":"Komatsu","year":"2003","journal-title":"Clin. Exp. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1099\/vir.0.031815-0","article-title":"Antigen-presenting cells of haematopoietic origin prime cytomegalovirus-specific CD8 T-cells but are not sufficient for driving memory inflation during viral latency","volume":"92","author":"Seckert","year":"2011","journal-title":"J. Gen. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Torti, N., Walton, S.M., Brocker, T., R\u00fclicke, T., and Oxenius, A. (2011). Non-hematopoietic cells in lymph nodes drive memory CD8 T cell inflation during murine cytomegalovirus infection. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002313"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hutchinson, S., Sims, S., O\u2019Hara, G., Silk, J., Gileadi, U., Cerundolo, V., and Klenerman, P. (2011). A dominant role for the immunoproteasome in CD8+ T cell responses to murine cytomegalovirus. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0014646"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11879","DOI":"10.1073\/pnas.91.25.11879","article-title":"Human cytomegalovirus latent infection of granulocyte-macrophage progenitors","volume":"91","author":"Kondo","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6581","DOI":"10.1128\/jvi.65.12.6581-6588.1991","article-title":"Human cytomegalovirus productively infects primary differentiated macrophages","volume":"65","author":"Ibanez","year":"1991","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1099\/0022-1317-72-9-2059","article-title":"Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells","volume":"72","author":"Sissons","year":"1991","journal-title":"J. Gen. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1128\/JVI.72.1.95-103.1998","article-title":"Cellular localization of latent murine cytomegalovirus","volume":"72","author":"Koffron","year":"1998","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1006\/viro.1996.8303","article-title":"Latent murine cytomegalovirus infection in macrophages","volume":"227","author":"Pollock","year":"1997","journal-title":"Virology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4086","DOI":"10.1182\/blood.V86.11.4086.bloodjournal86114086","article-title":"Detection of cytomegalovirus DNA in CD34+ cells from blood and bone marrow","volume":"86","author":"Serr","year":"1995","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1099\/0022-1317-77-12-3099","article-title":"Detection of endogenous human cytomegalovirus in CD34+ bone marrow progenitors","volume":"77","author":"Mendelson","year":"1996","journal-title":"J. Gen. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3937","DOI":"10.1073\/pnas.95.7.3937","article-title":"Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells","volume":"95","author":"Hahn","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7543","DOI":"10.1128\/JVI.75.16.7543-7554.2001","article-title":"Reactivation of latent human cytomegalovirus in CD14(+) monocytes is differentiation dependent","volume":"75","author":"Streblow","year":"2001","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/S0046-8177(84)80076-3","article-title":"Widespread presence of histologically occult cytomegalovirus","volume":"15","author":"Myerson","year":"1984","journal-title":"Hum. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8869","DOI":"10.1128\/JVI.00870-09","article-title":"Liver sinusoidal endothelial cells are a site of murine cytomegalovirus latency and reactivation","volume":"83","author":"Seckert","year":"2009","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Van den Berg, S.P.H., Pardieck, I.N., Lanfermeijer, J., Sauce, D., Klenerman, P., van Baarle, D., and Arens, R. (2019). The hallmarks of CMV-specific CD8 T-cell differentiation. Med. Microbiol. Immunol.","DOI":"10.1007\/s00430-019-00608-7"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4077","DOI":"10.1172\/JCI42758","article-title":"Molecular profiling of cytomegalovirus-induced human CD8+ T cell differentiation","volume":"120","author":"Hertoghs","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"197","DOI":"10.3389\/fimmu.2019.00197","article-title":"Inflation vs. Exhaustion of Antiviral CD8+ T-Cell Populations in Persistent Infections: Two Sides of the Same Coin?","volume":"10","author":"Marchi","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5838","DOI":"10.4049\/jimmunol.169.10.5838","article-title":"Proliferation requirements of cytomegalovirus-specific, effector-type human CD8+ T cells","volume":"169","author":"Gamadia","year":"2002","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nature12519","article-title":"Immune clearance of highly pathogenic SIV infection","volume":"502","author":"Hansen","year":"2013","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/nm.1935","article-title":"Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge","volume":"15","author":"Hansen","year":"2009","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1237874","DOI":"10.1126\/science.1237874","article-title":"Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms","volume":"340","author":"Hansen","year":"2013","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1126\/science.aac9475","article-title":"Broadly targeted CD8+ T cell responses restricted by major histocompatibility complex E","volume":"351","author":"Hansen","year":"2016","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nature10003","article-title":"Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine","volume":"473","author":"Hansen","year":"2011","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tsuda, Y., Caposio, P., Parkins, C.J., Botto, S., Messaoudi, I., Cicin-Sain, L., Feldmann, H., and Jarvis, M.A. (2011). A Replicating Cytomegalovirus-Based Vaccine Encoding a Single Ebola Virus Nucleoprotein CTL Epitope Confers Protection against Ebola Virus. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001275"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1016\/j.vaccine.2015.03.029","article-title":"A cytomegalovirus-based vaccine provides long-lasting protection against lethal Ebola virus challenge after a single dose","volume":"33","author":"Tsuda","year":"2015","journal-title":"Vaccine"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"21674","DOI":"10.1038\/srep21674","article-title":"Cytomegalovirus-based vaccine expressing Ebola virus glycoprotein protects nonhuman primates from Ebola virus infection","volume":"6","author":"Marzi","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/nm.4473","article-title":"Prevention of tuberculosis in rhesus macaques by a cytomegalovirus-based vaccine","volume":"24","author":"Hansen","year":"2018","journal-title":"Nat. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.4049\/jimmunol.1302523","article-title":"A Novel Murine Cytomegalovirus Vaccine Vector Protects against Mycobacterium tuberculosis","volume":"193","author":"Beverley","year":"2014","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"M\u00e9ndez, A.C., Rodr\u00edguez-Rojas, C., and Del Val, M. (2019). Vaccine vectors: The bright side of cytomegalovirus. Med. Microbiol. Immunol.","DOI":"10.1007\/s00430-019-00597-7"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1128\/JVI.78.5.2255-2264.2004","article-title":"Expansion of Protective CD8+ T-Cell Responses Driven by Recombinant Cytomegaloviruses","volume":"78","author":"Karrer","year":"2004","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.vaccine.2005.07.070","article-title":"Replication and immunoactivity of the recombinant Peromyscus maniculatus cytomegalovirus expressing hantavirus G1 glycoprotein in vivo and in vitro","volume":"24","author":"Rizvanov","year":"2006","journal-title":"Vaccine"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"12203","DOI":"10.1128\/JVI.77.22.12203-12210.2003","article-title":"Generation of a Recombinant Cytomegalovirus for Expression of a Hantavirus Glycoprotein","volume":"77","author":"Rizvanov","year":"2003","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/mi.2016.48","article-title":"Intranasal administration of RSV antigen-expressing MCMV elicits robust tissue-resident effector and effector memory CD8+ T cells in the lung","volume":"10","author":"Morabito","year":"2017","journal-title":"Mucosal Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1111\/apt.13124","article-title":"Review article: Cytomegalovirus and inflammatory bowel disease","volume":"41","author":"Sager","year":"2015","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_53","first-page":"1437","article-title":"Cytomegalovirus Infection in Cardiovascular Diseases","volume":"83","author":"Lebedeva","year":"2018","journal-title":"Biochemistry"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e005025","DOI":"10.1161\/JAHA.116.005025","article-title":"Cytomegalovirus Infection and Relative Risk of Cardiovascular Disease (Ischemic Heart Disease, Stroke, and Cardiovascular Death): A Meta-Analysis of Prospective Studies Up to 2016","volume":"6","author":"Wang","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Simanek, A.M., Dowd, J.B., Pawelec, G., Melzer, D., Dutta, A., and Aiello, A.E. (2011). Seropositivity to cytomegalovirus, inflammation, all-cause and cardiovascular disease-related mortality in the United States. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016103"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1097\/CJI.0b013e3182585d50","article-title":"A cytomegalovirus-based vaccine expressing a single tumor-specific CD8+ T-cell epitope delays tumor growth in a murine model of prostate cancer","volume":"35","author":"Klyushnenkova","year":"2012","journal-title":"J. Immunother."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Dekhtiarenko, I., Ratts, R.B., Blatnik, R., Lee, L.N., Fischer, S., Borkner, L., Oduro, J.D., Marandu, T.F., Hoppe, S., and Ruzsics, Z. (2016). Peptide Processing Is Critical for T-Cell Memory Inflation and May Be Optimized to Improve Immune Protection by CMV-Based Vaccine Vectors. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1006072"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s40425-019-0500-9","article-title":"Demarcated thresholds of tumor-specific CD8 T cells elicited by MCMV-based vaccine vectors provide robust correlates of protection","volume":"7","author":"Ratts","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.3389\/fimmu.2017.01993","article-title":"Combining Adoptive Cell Therapy with Cytomegalovirus-Based Vaccine Is Protective against Solid Skin Tumors","volume":"8","author":"Grenier","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1080\/21645515.2017.1331795","article-title":"Intratumoral infection by CMV may change the tumor environment by directly interacting with tumor-associated macrophages to promote cancer immunity","volume":"13","author":"Erkes","year":"2017","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1002\/eji.201746964","article-title":"Cytomegalovirus vector expressing RAE-1\u03b3 induces enhanced anti-tumor capacity of murine CD8+ T cells","volume":"47","author":"Lemmermann","year":"2017","journal-title":"Eur. J. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.bbrc.2013.06.068","article-title":"Cytomegalovirus-based cancer vaccines expressing TRP2 induce rejection of melanoma in mice","volume":"437","author":"Xu","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1158\/2326-6066.CIR-14-0044","article-title":"Cytomegalovirus-Based Vaccine Expressing a Modified Tumor Antigen Induces Potent Tumor-Specific CD8(+) T-cell Response and Protects Mice from Melanoma","volume":"3","author":"Qiu","year":"2015","journal-title":"Cancer Immunol. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1038\/mt.2016.121","article-title":"Intratumoral Infection with Murine Cytomegalovirus Synergizes with PD-L1 Blockade to Clear Melanoma Lesions and Induce Long-term Immunity","volume":"24","author":"Erkes","year":"2016","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"29392","DOI":"10.18632\/oncotarget.25630","article-title":"Fc\u03b3RI expression on macrophages is required for antibody-mediated tumor protection by cytomegalovirus-based vaccines","volume":"9","author":"Benonisson","year":"2018","journal-title":"Oncotarget"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7730","DOI":"10.1128\/JVI.02696-09","article-title":"A Spread-Deficient Cytomegalovirus for Assessment of First-Target Cells in Vaccination","volume":"84","author":"Mohr","year":"2010","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"9254","DOI":"10.1128\/JVI.00443-11","article-title":"M94 is Essential for the Secondary Envelopment of Murine Cytomegalovirus","volume":"85","author":"Maninger","year":"2011","journal-title":"J. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Snyder, C.M., Allan, J.E., Bonnett, E.L., Doom, C.M., and Hill, A.B. (2010). Cross-Presentation of a Spread-Defective MCMV Is Sufficient to Prime the Majority of Virus-Specific CD8+ T Cells. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009681"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Snyder, C.M., Cho, K.S., Bonnett, E.L., Allan, J.E., and Hill, A.B. (2011). Sustained CD8+ T Cell Memory Inflation after Infection with a Single-Cycle Cytomegalovirus. PLOS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002295"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Herbein, G. (2018). The Human Cytomegalovirus, from Oncomodulation to Oncogenesis. Viruses, 10.","DOI":"10.3390\/v10080408"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1593\/neo.81178","article-title":"The Story of Human Cytomegalovirus and Cancer: Increasing Evidence and Open Questions","volume":"11","author":"Michaelis","year":"2009","journal-title":"Neoplasia"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0042-6822(73)81007-4","article-title":"Malignant transformation of hamster embryo fibroblasts following exposure to ultraviolet-irradiated human cytomegalovirus","volume":"55","author":"Albrecht","year":"1973","journal-title":"Virology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1126\/science.179143","article-title":"Oncogenic transformation of human embryo lung cells by human cytomegalovirus","volume":"192","author":"Geder","year":"1976","journal-title":"Science"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1093\/jnci\/58.4.1003","article-title":"Human cells transformed in vitro by human cytomegalovirus: Tumorigenicity in athymic nude mice","volume":"58","author":"Geder","year":"1977","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_75","first-page":"591","article-title":"Alterations in biological properties of different lines of cytomegalorivus-transformed human embryo lung cells following in vitro cultivation","volume":"00324","author":"Geder","year":"1978","journal-title":"IARC Sci. Publ."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1126\/science.1152095","article-title":"Phosphorylation of Retinoblastoma Protein by Viral Protein with Cyclin-Dependent Kinase Function","volume":"320","author":"Hume","year":"2008","journal-title":"Science"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"8390","DOI":"10.1128\/JVI.00505-06","article-title":"Potential Role for p53 in the Permissive Life Cycle of Human Cytomegalovirus","volume":"80","author":"Casavant","year":"2006","journal-title":"J. Virol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1158\/0008-5472.CAN-07-2291","article-title":"Modulation of Oncogenic Phenotype in Human Glioma Cells by Cytomegalovirus IE1\u2013Mediated Mitogenicity","volume":"68","author":"Cobbs","year":"2008","journal-title":"Cancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1182\/blood-2010-06-291245","article-title":"IL-6 in human cytomegalovirus secretome promotes angiogenesis and survival of endothelial cells through the stimulation of survivin","volume":"117","author":"Botto","year":"2011","journal-title":"Blood"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/cei.12785","article-title":"Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans","volume":"185","author":"Bigley","year":"2016","journal-title":"Clin. Exp. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5326","DOI":"10.1158\/0008-5472.CAN-16-1162","article-title":"Identification of a Natural Killer Cell Receptor Allele That Prolongs Survival of Cytomegalovirus-Positive Glioblastoma Patients","volume":"76","author":"Rahman","year":"2016","journal-title":"Cancer Res."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Yang, C.-F., Ho, H.-L., Lin, S.-C., Hsu, C.-Y., and Ho, D.M.-T. (2017). Detection of human cytomegalovirus in glioblastoma among Taiwanese subjects. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179366"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1002\/jmv.24450","article-title":"Expanding role of cytomegalovirus as a human pathogen","volume":"88","author":"Navarro","year":"2016","journal-title":"J. Med. Virol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1093\/neuonc\/nou167","article-title":"Human cytomegalovirus infection in tumor cells of the nervous system is not detectable with standardized pathologico-virological diagnostics","volume":"16","author":"Baumgarten","year":"2014","journal-title":"Neuro Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1038\/modpathol.3800352","article-title":"Lack of association of cytomegalovirus with human brain tumors","volume":"18","author":"Lau","year":"2005","journal-title":"Mod. Pathol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jcv.2012.12.018","article-title":"Human cytomegalovirus infection levels in glioblastoma multiforme are of prognostic value for survival","volume":"57","author":"Rahbar","year":"2013","journal-title":"J. Clin. Virol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1002\/ijc.29042","article-title":"Absence of cytomegalovirus in high-coverage DNA sequencing of human glioblastoma multiforme","volume":"136","author":"Tang","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/j.tranon.2018.08.003","article-title":"Impact of Human Cytomegalovirus Infection and its Immune Response on Survival of Patients with Ovarian Cancer","volume":"11","author":"Estekizadeh","year":"2018","journal-title":"Transl. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0304-3835(03)00269-6","article-title":"Human herpes viruses in non-melanoma skin cancers","volume":"198","author":"Zafiropoulos","year":"2003","journal-title":"Cancer Lett."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1016\/S0140-6736(02)11524-8","article-title":"Specific localisation of human cytomegalovirus nucleic acids and proteins in human colorectal cancer","volume":"360","author":"Harkins","year":"2002","journal-title":"Lancet Lond. Engl."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"5669","DOI":"10.1158\/0008-5472.CAN-12-2425","article-title":"Cytomegalovirus Infection Leads to Pleomorphic Rhabdomyosarcomas in Trp53+\/\u2212 Mice","volume":"72","author":"Price","year":"2012","journal-title":"Cancer Res."},{"key":"ref_92","first-page":"3347","article-title":"Human Cytomegalovirus Infection and Expression in Human Malignant Glioma","volume":"62","author":"Cobbs","year":"2002","journal-title":"Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6473","DOI":"10.1158\/1078-0432.CCR-13-1121","article-title":"Cidofovir: A Novel Antitumor Agent for Glioblastoma","volume":"19","author":"Hadaczek","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1002\/ijc.28111","article-title":"Effects of valganciclovir as an add-on therapy in patients with cytomegalovirus-positive glioblastoma: A randomized, double-blind, hypothesis-generating study","volume":"133","author":"Stragliotto","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1056\/NEJMc1302145","article-title":"Survival in patients with glioblastoma receiving valganciclovir","volume":"369","author":"Rahbar","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1084\/jem.20120696","article-title":"Antiviral drug ganciclovir is a potent inhibitor of microglial proliferation and neuroinflammation","volume":"211","author":"Ding","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"(2019, June 26). Altered Development of the Brain after Focal Herpesvirus Infection of the Central Nervous System | JEM. Available online: http:\/\/jem.rupress.org\/content\/205\/2\/423.","DOI":"10.1084\/jem.20071489"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1158\/0008-5472.CAN-12-3846","article-title":"Cytomegalovirus Contributes to Glioblastoma in the Context of Tumor Suppressor Mutations","volume":"73","author":"Price","year":"2013","journal-title":"Cancer Res."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Krenzlin, H., Behera, P., Lorenz, V., Passaro, C., Zdioruk, M., Nowicki, M.O., Grauwet, K., Zhang, H., Skubal, M., and Ito, H. (2019). Cytomegalovirus promotes murine glioblastoma growth via pericyte recruitment and angiogenesis. J. Clin. Investig., 130.","DOI":"10.1172\/JCI123375"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Yang, Z., Tang, X., Meng, G., Benesch, M.G.K., Mackova, M., Belon, A.P., Serrano-Lomelin, J., Goping, I.S., Brindley, D.N., and Hemmings, D.G. (2019). Latent Cytomegalovirus Infection in Female Mice Increases Breast Cancer Metastasis. Cancers, 11.","DOI":"10.3390\/cancers11040447"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4801","DOI":"10.1128\/JVI.80.10.4801-4819.2006","article-title":"Lymphoma Cell Apoptosis in the Liver Induced by Distant Murine Cytomegalovirus Infection","volume":"80","author":"Erlach","year":"2006","journal-title":"J. Virol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2857","DOI":"10.1128\/JVI.76.6.2857-2870.2002","article-title":"Tumor Control in a Model of Bone Marrow Transplantation and Acute Liver-Infiltrating B-Cell Lymphoma: An Unpredicted Novel Function of Cytomegalovirus","volume":"76","author":"Erlach","year":"2002","journal-title":"J. Virol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s00430-015-0408-z","article-title":"Mechanism of tumor remission by cytomegalovirus in a murine lymphoma model: Evidence for involvement of virally induced cellular interleukin-15","volume":"204","author":"Erlach","year":"2015","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"283ra52","DOI":"10.1126\/scitranslmed.aaa4306","article-title":"STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade","volume":"7","author":"Fu","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Wilski, N.A., Del Casale, C., Purwin, T.J., Aplin, A.E., and Snyder, C.M. (2019). Murine cytomegalovirus infection of melanoma lesions delays tumor growth by recruiting and re-polarizing monocytic phagocytes in the tumor. BiorXiv.","DOI":"10.1101\/597948"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nrclinonc.2016.217","article-title":"Tumor-Associated Macrophages as Treatment Targets in Oncology","volume":"14","author":"Mantovani","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.3390\/cancers6031670","article-title":"Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment","volume":"6","author":"Chanmee","year":"2014","journal-title":"Cancers"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Pathria, P., Louis, T.L., and Varner, J.A. (2019). Targeting Tumor-Associated Macrophages in Cancer. Trends Immunol.","DOI":"10.1016\/j.it.2019.02.003"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1084\/jem.20171440","article-title":"Rapid activation of tumor-associated macrophages boosts preexisting tumor immunity","volume":"215","author":"Hoves","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1084\/jem.20171435","article-title":"Myeloid-targeted immunotherapies act in synergy to induce inflammation and antitumor immunity","volume":"215","author":"Perry","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/2045-824X-4-14","article-title":"Myeloid cells in tumor inflammation","volume":"4","author":"Schmid","year":"2012","journal-title":"Vasc. Cell"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"96496","DOI":"10.18632\/oncotarget.20410","article-title":"Macrophage depletion through colony stimulating factor 1 receptor pathway blockade overcomes adaptive resistance to anti-VEGF therapy","volume":"8","author":"Lyons","year":"2017","journal-title":"Oncotarget"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Jarosz-Biej, M., Kami\u0144ska, N., Matuszczak, S., Cicho\u0144, T., Pamu\u0142a-Pi\u0142at, J., Czapla, J., Smolarczyk, R., Skwarzy\u0144ska, D., Kulik, K., and Szala, S. (2018). M1-like macrophages change tumor blood vessels and microenvironment in murine melanoma. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191012"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Genin, M., Clement, F., Fattaccioli, A., Raes, M., and Michiels, C. (2015). M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1546-9"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1128\/JVI.01585-12","article-title":"Human cytomegalovirus infection of M1 and M2 macrophages triggers inflammation and autologous T-cell proliferation","volume":"87","author":"Bayer","year":"2013","journal-title":"J. Virol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.virusres.2009.04.026","article-title":"NF-\u03baB and Phosphatidylinositol 3-Kinase Activity Mediates the HCMV-Induced Atypical M1\/M2 Polarization of Monocytes","volume":"144","author":"Chan","year":"2009","journal-title":"Virus Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"698","DOI":"10.4049\/jimmunol.181.1.698","article-title":"Transcriptome analysis reveals human cytomegalovirus reprograms monocyte differentiation toward an M1 macrophage","volume":"181","author":"Chan","year":"2008","journal-title":"J. Immunol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1182\/blood-2005-05-1833","article-title":"Cytomegalovirus MCK-2 controls mobilization and recruitment of myeloid progenitor cells to facilitate dissemination","volume":"107","author":"Noda","year":"2006","journal-title":"Blood"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"9966","DOI":"10.1128\/JVI.75.20.9966-9976.2001","article-title":"Murine Cytomegalovirus CC Chemokine Homolog MCK-2 (m131-129) Is a Determinant of Dissemination That Increases Inflammation at Initial Sites of Infection","volume":"75","author":"Saederup","year":"2001","journal-title":"J. Virol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.virol.2006.04.031","article-title":"Genes of murine cytomegalovirus exist as a number of distinct genotypes","volume":"352","author":"Smith","year":"2006","journal-title":"Virology"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"6689","DOI":"10.1128\/JVI.00160-08","article-title":"Laboratory strains of murine cytomegalovirus are genetically similar to but phenotypically distinct from wild strains of virus","volume":"82","author":"Smith","year":"2008","journal-title":"J. Virol."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/7\/3\/62\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:03:46Z","timestamp":1760187826000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/7\/3\/62"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,9]]},"references-count":121,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["vaccines7030062"],"URL":"https:\/\/doi.org\/10.3390\/vaccines7030062","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,9]]}}}