{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T02:13:52Z","timestamp":1784945632549,"version":"3.55.0"},"reference-count":129,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Extranodal NK\/T-Cell Lymphoma, nasal type (ENKTL-NT) has some salient aspects. The lymphoma is commonly seen in Eastern Asia, has progressive necrotic lesions in the nasal cavity, makes midfacial destructive lesions, and shows poor prognosis. The lymphoma cell is originated from either NK- or \u03b3\u03b4 T-cells, which express CD56. Since the authors first demonstrated the existence of Epstein\u2013Barr virus (EBV) DNA and EBV oncogenic proteins in lymphoma cells, ENKTL-NT has been recognized as an EBV-associated malignancy. Because the angiocentric and polymorphous lymphoma cells are mixed with inflammatory cells on a necrotic background, the diagnosis of ENKTL-NT requires CD56 immunostaining and EBER in situ hybridization. In addition, serum the EBV DNA level is useful for the diagnosis and monitoring of ENKTL-NT. Although ENKTL-NT is refractory lymphoma, the prognosis is improved by the development of therapies such as concomitant chemoradiotherapy. The basic research reveals that a wide variety of intracellular\/cell surface molecules, cytokines, chemokines, and micro RNAs are involved in lymphomagenesis, and some of them are related to EBV. Understanding lymphoma behavior introduces new therapeutic strategies, such as the usage of immune checkpoint inhibitors, peptide vaccines, and molecular targeting therapy. This review addresses recent advances in basic and clinical aspects of ENKTL-NT, especially its relation to EBV features.<\/jats:p>","DOI":"10.3390\/microorganisms9071381","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T11:07:40Z","timestamp":1624619260000},"page":"1381","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Extranodal NK\/T-Cell Lymphoma, Nasal Type: Genetic, Biologic, and Clinical Aspects with a Central Focus on Epstein\u2013Barr Virus Relation"],"prefix":"10.3390","volume":"9","author":[{"given":"Miki","family":"Takahara","sequence":"first","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa 078-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Kumai","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa 078-8510, Japan"},{"name":"Department of Innovative Head & Neck Cancer Research and Treatment (IHNCRT), Asahikawa Medical University, Asahikawa 078-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Kishibe","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa 078-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8326-8296","authenticated-orcid":false,"given":"Toshihiro","family":"Nagato","sequence":"additional","affiliation":[{"name":"Department of Pathology, Asahikawa Medical University, Asahikawa 078-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuaki","family":"Harabuchi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa 078-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/0140-6736(90)90002-M","article-title":"Epstein-Barr virus in nasal T-cell lymphomas in patients with lethal midline granuloma","volume":"335","author":"Harabuchi","year":"1990","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1002\/(SICI)1097-0142(19960515)77:10<2137::AID-CNCR27>3.0.CO;2-V","article-title":"Nasal T-cell lymphoma causally associated with Epstein-Barr virus: Clinicopathologic, phenotypic, and genotypic studies","volume":"77","author":"Harabuchi","year":"1996","journal-title":"Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1200\/JCO.2005.04.1384","article-title":"Extranodal natural killer T-cell lymphoma, nasal-type: A prognostic model from a retrospective multicenter study","volume":"24","author":"Lee","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/ijc.2910440112","article-title":"Nation-wide study of lethal mid-line granuloma in Japan: Frequencies of Wegener\u2019s granulomatosis, polymorphic reticulosis, malignant lymphoma and other related conditions","volume":"44","author":"Aozasa","year":"1989","journal-title":"Int. J. Cancer"},{"key":"ref_5","first-page":"55","article-title":"Characteristics of nasal T\/NK-cell lymphoma among Brazilians","volume":"49","author":"Altemani","year":"2002","journal-title":"Neoplasma"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1097\/00000478-200011000-00006","article-title":"Sinonasal NK\/T-cell lymphomas in the United States","volume":"24","author":"Gaal","year":"2000","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1177\/000348949910800417","article-title":"Sinonasal malignant lymphomas: A distinct clinicopathological category","volume":"108","author":"Vidal","year":"1999","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1182\/blood.V81.10.2688.2688","article-title":"Nasal T-cell lymphoma: A clinicopathologic entity associated with peculiar phenotype and with Epstein-Barr virus","volume":"81","author":"Kanavaros","year":"1993","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1177\/000348948509400223","article-title":"Midfacial T cell lymphoma: Characterization by monoclonal antibodies","volume":"94","author":"Yamanaka","year":"1985","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1182\/blood.V84.5.1361.1361","article-title":"A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group","volume":"84","author":"Harris","year":"1994","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/0002-9610(66)90328-X","article-title":"Primary lymphoma of the nose including a relationship to lethal midline granuloma","volume":"112","author":"Eichel","year":"1966","journal-title":"Am. J. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1182\/blood.V87.4.1466.bloodjournal8741466","article-title":"CD5-CD56+ T-cell receptor silent peripheral T-cell lymphomas are natural killer cell lymphomas","volume":"87","author":"Emile","year":"1996","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1182\/blood.V97.3.708","article-title":"Characterization of novel natural killer (NK)-cell and gammadelta T-cell lines established from primary lesions of nasal T\/NK-cell lymphomas associated with the Epstein-Barr virus","volume":"97","author":"Nagata","year":"2001","journal-title":"Blood"},{"key":"ref_14","first-page":"S104","article-title":"The role of morphologic features, phenotype, genotype, and anatomic site in defining extranodal T-cell or NK-cell neoplasms","volume":"111","author":"Kinney","year":"1999","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1002\/hon.847","article-title":"Extranodal NK\/T-cell lymphoma: Diagnosis and treatment cues","volume":"26","author":"Suzuki","year":"2008","journal-title":"Hematol. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s10147-009-0882-7","article-title":"Nasal natural killer (NK)\/T-cell lymphoma: Clinical, histological, virological, and genetic features","volume":"14","author":"Harabuchi","year":"2009","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1099\/0022-1317-75-1-77","article-title":"Clonality, expression and methylation patterns of the Epstein-Barr virus genomes in lethal midline granulomas classified as peripheral angiocentric T cell lymphomas","volume":"75","author":"Minarovits","year":"1994","journal-title":"J. Gen. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3389\/fped.2019.00141","article-title":"Extranodal Natural Killer\/T-Cell Lymphoma, Nasal Type: Basic Science and Clinical Progress","volume":"7","author":"Harabuchi","year":"2019","journal-title":"Front. Pediatr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1002\/jmv.20853","article-title":"Clinical usefulness of serum EBV DNA levels of BamHI W and LMP1 for Nasal NK\/T-cell lymphoma","volume":"79","author":"Ishii","year":"2007","journal-title":"J. Med. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3960\/jslrt.41.93","article-title":"Treatment outcome of nasal NK-cell lymphoma: A case report of 12 consecutively-diagnosed cases and a review of the literature","volume":"41","author":"Yamaguchi","year":"2001","journal-title":"J. Clin. Exp. Hematopathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/hon.2273","article-title":"Novel treatment for early-stage nasal natural killer\/T-cell lymphoma: Intra-maxillary arterial infusion chemotherapy with concomitant radiotherapy","volume":"35","author":"Takahara","year":"2017","journal-title":"Hematol. Oncol."},{"key":"ref_22","first-page":"64","article-title":"Photographs of a case of rapid destruction of the nose and face","volume":"12","author":"McBride","year":"1897","journal-title":"J. Laryngol. Otol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1177\/000348944905800405","article-title":"Lethal granulomatous ulceration, involving midline facial tissues","volume":"58","author":"Williams","year":"1949","journal-title":"Ann. Otol. Rhino. Laryngol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1002\/1097-0142(19920815)70:4<835::AID-CNCR2820700419>3.0.CO;2-F","article-title":"Lethal midline granuloma (peripheral T-cell lymphoma) after lymphomatoid papulosis","volume":"70","author":"Harabuchi","year":"1992","journal-title":"Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/S0046-8177(87)80410-0","article-title":"Expression of natural killer cell markers in non-Hodgkin\u2019s lymphomas","volume":"18","author":"Ng","year":"1987","journal-title":"Hum. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1002\/1097-0142(19821201)50:11<2336::AID-CNCR2820501120>3.0.CO;2-C","article-title":"Nasal T-cell lymphoma as a type of so-called \u201clethal midline granuloma\u201d","volume":"50","author":"Ishii","year":"1982","journal-title":"Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/hon.2900080505","article-title":"Presence of Epstein-Barr virus DNA in nasal lymphomas of B and \u2018T\u2019 cell type","volume":"8","author":"Ho","year":"1990","journal-title":"Hematol. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1097\/00000478-199205000-00002","article-title":"Localization of Epstein-Barr viral genomes in angiocentric immunoproliferative lesions","volume":"16","author":"Medeiros","year":"1992","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1097\/00000478-199202000-00008","article-title":"Frequency of Epstein-Barr viral DNA in \u201cWestern\u201d sinonasal and Waldeyer\u2019s ring non-Hodgkin\u2019s lymphoma","volume":"16","author":"Weiss","year":"1992","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_30","first-page":"3055","article-title":"Pathological and clinical characteristics of 1,248 non-Hodgkin\u2019s lymphomas from a regional cancer hospital in Shandong, China","volume":"12","author":"Liu","year":"2011","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4124","DOI":"10.1200\/JCO.2008.16.4558","article-title":"International peripheral T-cell and natural killer\/T-cell lymphoma study: Pathology findings and clinical outcomes","volume":"26","author":"Vose","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1093\/annonc\/mdf033","article-title":"Peripheral T-cell lymphoma (excluding anaplastic large-cell lymphoma): Results from the Non-Hodgkin\u2019s Lymphoma Classification Project","volume":"13","author":"Rudiger","year":"2002","journal-title":"Ann. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/1750-1172-8-95","article-title":"Aggressive mature natural killer cell neoplasms: From epidemiology to diagnosis","volume":"8","author":"Lima","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1007\/s11899-016-0355-9","article-title":"Extranodal NK\/T Cell Lymphoma, Nasal Type (ENKTL-NT): An Update on Epidemiology, Clinical Presentation, and Natural History in North American and European Cases","volume":"11","author":"Haverkos","year":"2016","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1093\/jnci\/94.23.1780","article-title":"Association of HLA class I and II alleles and extended haplotypes with nasopharyngeal carcinoma in Taiwan","volume":"94","author":"Hildesheim","year":"2002","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1046\/j.0307-7772.2001.00529.x","article-title":"HLA associations with nasopharyngeal carcinoma in Southern Chinese: A meta-analysis","volume":"27","author":"Goldsmith","year":"2002","journal-title":"Clin. Otolaryngol. Allied Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3310","DOI":"10.1182\/blood-2007-05-086934","article-title":"HLA-A*02 is associated with a reduced risk and HLA-A*01 with an increased risk of developing EBV+ Hodgkin lymphoma","volume":"110","author":"Niens","year":"2007","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1128\/JVI.03001-14","article-title":"Epstein-Barr virus type 2 latently infects T cells, inducing an atypical activation characterized by expression of lymphotactic cytokines","volume":"89","author":"Coleman","year":"2015","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/978-981-10-7230-7_21","article-title":"EBV in T-\/NK-Cell Tumorigenesis","volume":"1045","author":"Kimura","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1159\/000106462","article-title":"Selected amino acid change encoding Epstein-Barr virus-specific T cell epitope of the LMP2A gene in Japanese nasal NK\/T cell lymphoma patients","volume":"50","author":"Nagamine","year":"2007","journal-title":"Intervirology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s11262-006-0008-5","article-title":"Sequence variations of Epstein-Barr virus LMP1 gene in nasal NK\/T-cell lymphoma","volume":"34","author":"Nagamine","year":"2007","journal-title":"Virus Genes"},{"key":"ref_42","first-page":"932","article-title":"Analysis of clinicopathological features and prognostic factors of 62 nasal NK\/T-cell lymphomas","volume":"21","author":"Xu","year":"2007","journal-title":"J. Clin. Otorhinolaryngol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/1096-8652(200102)66:2<145::AID-AJH1033>3.0.CO;2-V","article-title":"Familial nasal NK\/T-cell lymphoma and pesticide use","volume":"66","author":"Kojya","year":"2001","journal-title":"Am. J. Hematol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1093\/annonc\/mdp418","article-title":"Prognostic factors for mature natural killer (NK) cell neoplasms: Aggressive NK cell leukemia and extranodal NK cell lymphoma, nasal type","volume":"21","author":"Suzuki","year":"2010","journal-title":"Ann. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.clon.2008.05.011","article-title":"A clinical study of 115 patients with extranodal natural killer\/T-cell lymphoma, nasal type","volume":"20","author":"Wu","year":"2008","journal-title":"Clin. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3785","DOI":"10.1182\/blood-2005-05-2056","article-title":"Local tumor invasiveness is more predictive of survival than International Prognostic Index in stage I(E)\/II(E) extranodal NK\/T-cell lymphoma, nasal type","volume":"106","author":"Kim","year":"2005","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1097\/PAS.0b013e31821ec4b5","article-title":"Clinicopathologic and molecular features of 122 Brazilian cases of nodal and extranodal NK\/T-cell lymphoma, nasal type, with EBV subtyping analysis","volume":"35","author":"Gualco","year":"2011","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.humpath.2003.08.025","article-title":"P53, N- and K-Ras, and beta-catenin gene mutations and prognostic factors in nasal NK\/T-cell lymphoma from Hokkaido, Japan","volume":"35","author":"Takahara","year":"2004","journal-title":"Hum. Pathol"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1177\/000348949610500809","article-title":"Circulating intercellular adhesion molecule-1 and its cellular expression in head and neck non-Hodgkin\u2019s lymphomas, including lethal midline granuloma","volume":"105","author":"Harabuchi","year":"1996","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1002\/1097-0142(19880815)62:4<705::AID-CNCR2820620410>3.0.CO;2-Z","article-title":"Lethal midline granuloma (polymorphic reticulosis) and lymphomatoid granulomatosis. Evidence for a monoclonal T-cell lymphoproliferative disorder","volume":"62","author":"Gaulard","year":"1988","journal-title":"Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1046\/j.1365-2133.1999.02718.x","article-title":"Nasal-type T\/natural killer cell angiocentric lymphoma, Epstein-Barr virus-associated, and showing clonal T-cell receptor gamma gene rearrangement","volume":"140","author":"Yoon","year":"1999","journal-title":"Br. J. Dermatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/(SICI)1097-0215(19961104)68:3<285::AID-IJC3>3.0.CO;2-Y","article-title":"Nasal NK- and T-cell lymphomas share the same type of Epstein-Barr virus latency as nasopharyngeal carcinoma and Hodgkin\u2019s disease","volume":"68","author":"Chiang","year":"1996","journal-title":"Int. J. Cancer"},{"key":"ref_53","first-page":"735","article-title":"Comparative analysis of NK\/T-cell lymphoma and peripheral T-cell lymphoma in Korea: Clinicopathological correlations and analysis of EBV strain type and 30-bp deletion variant LMP1","volume":"53","author":"Kim","year":"2003","journal-title":"Pathol. Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7825","DOI":"10.1128\/JVI.00445-07","article-title":"Epstein-Barr virus entry","volume":"81","year":"2007","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/nm0602-594","article-title":"Alternate replication in B cells and epithelial cells switches tropism of Epstein-Barr virus","volume":"8","author":"Borza","year":"2002","journal-title":"Nat. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nm830","article-title":"Epstein-Barr virus infection of polarized tongue and nasopharyngeal epithelial cells","volume":"9","author":"Tugizov","year":"2003","journal-title":"Nat. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1182\/blood.V85.3.744.bloodjournal853744","article-title":"Morphology, immunophenotype, and distribution of latently and\/or productively Epstein-Barr virus-infected cells in acute infectious mononucleosis: Implications for the interindividual infection route of Epstein-Barr virus","volume":"85","author":"Anagnostopoulos","year":"1995","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/modpathol.3800369","article-title":"Distribution and phenotype of Epstein-Barr virus-infected cells in human pharyngeal tonsils","volume":"18","author":"Hudnall","year":"2005","journal-title":"Mod. Pathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"865","DOI":"10.4049\/jimmunol.146.3.865","article-title":"Expression of CR2 (the C3dg\/EBV receptor, CD21) on normal human peripheral blood T lymphocytes","volume":"146","author":"Fischer","year":"1991","journal-title":"J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1182\/blood.V85.2.456.456","article-title":"Model of Epstein-Barr virus infection of human thymocytes: Expression of viral genome and impact on cellular receptor expression in the T-lymphoblastic cell line, HPB-ALL","volume":"85","author":"Paterson","year":"1995","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1093\/intimm\/11.11.1841","article-title":"Expression of CD21 is developmentally regulated during thymic maturation of human T lymphocytes","volume":"11","author":"Fischer","year":"1999","journal-title":"Int. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.mehy.2004.03.012","article-title":"Clonal expansion of multiphenotypic Epstein-Barr virus-infected lymphocytes in chronic active Epstein-Barr virus infection","volume":"63","author":"Endo","year":"2004","journal-title":"Med. Hypotheses"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jcv.2011.01.014","article-title":"Clonal origin of Epstein-Barr virus (EBV)-infected T\/NK-cell subpopulations in EBV-positive T\/NK-cell lymphoproliferative disorders of childhood","volume":"51","author":"Ohga","year":"2011","journal-title":"J. Clin. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Smith, N.A., Coleman, C.B., Gewurz, B.E., and Rochford, R. (2020). CD21 (Complement Receptor 2) Is the Receptor for Epstein-Barr Virus Entry into T Cells. J. Virol., 94.","DOI":"10.1128\/JVI.00428-20"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5993","DOI":"10.4049\/jimmunol.170.12.5993","article-title":"Acquisition of viral receptor by NK cells through immunological synapse","volume":"170","author":"Tabiasco","year":"2003","journal-title":"J. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.cellimm.2018.01.011","article-title":"CD21-independent Epstein-Barr virus entry into NK cells","volume":"327","author":"Lee","year":"2018","journal-title":"Cell Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/ni0903-815","article-title":"What is trogocytosis and what is its purpose?","volume":"4","author":"Joly","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1046\/j.1365-2141.1997.752711.x","article-title":"Clonal chromosomal abnormalities as direct evidence for clonality in nasal T\/natural killer cell lymphomas","volume":"97","author":"Tien","year":"1997","journal-title":"Br. J. Haematol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1046\/j.1365-2141.1997.3223139.x","article-title":"Identification of del(6)(q21q25) as a recurring chromosomal abnormality in putative NK cell lymphoma\/leukaemia","volume":"98","author":"Wong","year":"1997","journal-title":"Br. J. Haematol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1016\/S0002-9440(10)64818-3","article-title":"Consistent patterns of allelic loss in natural killer cell lymphoma","volume":"157","author":"Siu","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1046\/j.1365-2141.2003.04419.x","article-title":"A 2.6 Mb interval on chromosome 6q25.2-q25.3 is commonly deleted in human nasal natural killer\/T-cell lymphoma","volume":"122","author":"Sun","year":"2003","journal-title":"Br. J. Haematol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4702","DOI":"10.1038\/sj.onc.1205571","article-title":"Frequent mutations of Fas gene in nasal NK\/T cell lymphoma","volume":"21","author":"Takakuwa","year":"2002","journal-title":"Oncogene"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1016\/S0002-9440(10)64490-2","article-title":"Frequent deletion of Fas gene sequences encoding death and transmembrane domains in nasal natural killer\/T-cell lymphoma","volume":"161","author":"Shen","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/labinvest.3780055","article-title":"Mutations of the p53 gene in nasal NK\/T-cell lymphoma","volume":"80","author":"Li","year":"2000","journal-title":"Lab. Investig."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/j.1349-7006.2003.tb01436.x","article-title":"Analysis of p53, K-ras, c-kit, and beta-catenin gene mutations in sinonasal NK\/T cell lymphoma in northeast district of China","volume":"94","author":"Hoshida","year":"2003","journal-title":"Cancer Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1016\/S0002-9440(10)63061-1","article-title":"p53 Mutations in nasal natural killer\/T-cell lymphoma from Mexico: Association with large cell morphology and advanced disease","volume":"159","author":"Kremer","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_77","first-page":"265","article-title":"p53, K-ras, c-kit and beta-catenin gene mutations in sinonasal NK\/T-cell lymphoma in Korea and Japan","volume":"13","author":"Hongyo","year":"2005","journal-title":"Oncol. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s13045-017-0452-9","article-title":"The diagnosis and management of NK\/T-cell lymphomas","volume":"10","author":"Tse","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1200\/JCO.2013.54.8800","article-title":"Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: The Lugano classification","volume":"32","author":"Cheson","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_80","first-page":"239","article-title":"Quantitative analysis of circulating cell-free Epstein-Barr virus (EBV) DNA levels in patients with EBV-associated lymphoid malignancies","volume":"111","author":"Lei","year":"2000","journal-title":"Br. J. Haematol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"6018","DOI":"10.1182\/blood-2011-05-354142","article-title":"Prospective measurement of Epstein-Barr virus-DNA in plasma and peripheral blood mononuclear cells of extranodal NK\/T-cell lymphoma, nasal type","volume":"118","author":"Suzuki","year":"2011","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1002\/hon.2360","article-title":"Circulating Epstein-Barr virus-encoded micro-RNAs as potential biomarkers for nasal natural killer\/T-cell lymphoma","volume":"35","author":"Komabayashi","year":"2017","journal-title":"Hematol. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"8250","DOI":"10.1158\/1078-0432.CCR-05-1426","article-title":"Expression of interleukin-9 in nasal natural killer\/T-cell lymphoma cell lines and patients","volume":"11","author":"Nagato","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"6771","DOI":"10.1158\/1078-0432.CCR-09-1052","article-title":"Production of interferon-{gamma}-inducible protein-10 and its role as an autocrine invasion factor in nasal natural killer\/T-cell lymphoma cells","volume":"15","author":"Moriai","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/ajh.23570","article-title":"Downregulation of miR-15a due to LMP1 promotes cell proliferation and predicts poor prognosis in nasal NK\/T-cell lymphoma","volume":"89","author":"Komabayashi","year":"2014","journal-title":"Am. J. Hematol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.exphem.2013.03.009","article-title":"Soluble ICAM-1 secretion and its functional role as an autocrine growth factor in nasal NK\/T cell lymphoma cells","volume":"41","author":"Takahara","year":"2013","journal-title":"Exp. Hematol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e976077","DOI":"10.4161\/2162402X.2014.976077","article-title":"c-Met is a novel tumor associated antigen for T-cell based immunotherapy against NK\/T cell lymphoma","volume":"4","author":"Kumai","year":"2015","journal-title":"Oncoimmunology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/s41374-018-0182-9","article-title":"Cyclin-dependent kinase 1 and survivin as potential therapeutic targets against nasal natural killer\/T-cell lymphoma","volume":"99","author":"Nagato","year":"2019","journal-title":"Lab. Investig."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1002\/ijc.22139","article-title":"Concomitant increase of LMP1 and CD25 (IL-2-receptor alpha) expression induced by IL-10 in the EBV-positive NK lines SNK6 and KAI3","volume":"119","author":"Takahara","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/bjh.12136","article-title":"Expression of CD70 in nasal natural killer\/T cell lymphoma cell lines and patients; its role for cell proliferation through binding to soluble CD27","volume":"160","author":"Yoshino","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s00262-015-1675-7","article-title":"CCL17 and CCL22\/CCR4 signaling is a strong candidate for novel targeted therapy against nasal natural killer\/T-cell lymphoma","volume":"64","author":"Kumai","year":"2015","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1002\/ijc.25969","article-title":"Monocytes enhance cell proliferation and LMP1 expression of nasal natural killer\/T-cell lymphoma cells by cell contact-dependent interaction through membrane-bound IL-15","volume":"130","author":"Ishii","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3109\/08830189809043001","article-title":"Interleukin 9 and its receptor: An overview of structure and function","volume":"16","author":"Demoulin","year":"1998","journal-title":"Int. Rev. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"5332","DOI":"10.1158\/0008-5472.CAN-04-0733","article-title":"Epstein-Barr virus (EBV)-encoded RNA promotes growth of EBV-infected T cells through interleukin-9 induction","volume":"64","author":"Yang","year":"2004","journal-title":"Cancer Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/0092-8674(87)90104-8","article-title":"Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1)","volume":"51","author":"Marlin","year":"1987","journal-title":"Cell"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4398","DOI":"10.4049\/jimmunol.147.12.4398","article-title":"Shedding of ICAM-1 from human melanoma cell lines induced by IFN-gamma and tumor necrosis factor-alpha. Functional consequences on cell-mediated cytotoxicity","volume":"147","author":"Becker","year":"1991","journal-title":"J. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4936","DOI":"10.1128\/JVI.79.8.4936-4943.2005","article-title":"Latent membrane protein 1 regulates STAT1 through NF-kappaB-dependent interferon secretion in Epstein-Barr virus-immortalized B cells","volume":"79","author":"Najjar","year":"2005","journal-title":"J. Virol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1084\/jem.177.6.1809","article-title":"Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells","volume":"177","author":"Taub","year":"1993","journal-title":"J. Exp. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1002\/ijc.20759","article-title":"The Epstein-Barr virus oncoprotein latent membrane protein 1 induces expression of the chemokine IP-10: Importance of mRNA half-life regulation","volume":"114","author":"Vockerodt","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"9150","DOI":"10.1073\/pnas.90.19.9150","article-title":"Epstein-Barr virus latent membrane protein 1 is essential for B-lymphocyte growth transformation","volume":"90","author":"Kaye","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/0092-8674(85)90256-9","article-title":"An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells","volume":"43","author":"Wang","year":"1985","journal-title":"Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1099\/0022-1317-76-11-2669","article-title":"Domains of the Epstein-Barr virus nuclear antigen 2 (EBNA2) involved in the transactivation of the latent membrane protein 1 and the EBNA Cp promoters","volume":"76","author":"Nerstedt","year":"1995","journal-title":"J. Gen. Virol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1002\/ijc.20654","article-title":"In vitro EBV-infected subline of KMH2, derived from Hodgkin lymphoma, expresses only EBNA-1, while CD40 ligand and IL-4 induce LMP-1 but not EBNA-2","volume":"113","author":"Kis","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3531","DOI":"10.1182\/blood.V93.10.3531.410k32_3531_3539","article-title":"Human monocytes constitutively express membrane-bound, biologically active, and interferon-gamma-upregulated interleukin-15","volume":"93","author":"Musso","year":"1999","journal-title":"Blood"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"R88","DOI":"10.1186\/ar1955","article-title":"Interleukin-15 and interferon-gamma participate in the cross-talk between natural killer and monocytic cells required for tumour necrosis factor production","volume":"8","author":"Ortiz","year":"2006","journal-title":"Arthritis Res. Ther."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1002\/1097-0142(19951201)76:11<2351::AID-CNCR2820761125>3.0.CO;2-1","article-title":"Frequent expression of P-glycoprotein\/MDR1 by nasal T-cell lymphoma cells","volume":"76","author":"Yamaguchi","year":"1995","journal-title":"Cancer"},{"key":"ref_109","first-page":"1","article-title":"Advances in the management of hemophagocytic lymphohistiocytosis","volume":"72","author":"Imashuku","year":"2000","journal-title":"Int. J. Hematol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1111\/j.1349-7006.2008.00768.x","article-title":"Phase I study of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)\/T-cell lymphoma and leukemia","volume":"99","author":"Yamaguchi","year":"2008","journal-title":"Cancer Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"4044","DOI":"10.1200\/JCO.2012.45.6541","article-title":"Concurrent chemoradiotherapy for localized nasal natural killer\/T-cell lymphoma: An updated analysis of the Japan Clinical Oncology Group study JCOG0211","volume":"30","author":"Yamaguchi","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s12185-019-02609-x","article-title":"JSH practical guidelines for hematological malignancies, 2018: II. Lymphoma-9. Extranodal NK\/T-cell lymphoma, nasal type (ENKL)","volume":"109","author":"Yamaguchi","year":"2019","journal-title":"Int. J. Hematol."},{"key":"ref_113","unstructured":"(2021, May 29). NCCN Guidelines T-Cell Lymphomas Version 1.2021. Available online: www.nccn.org\/patients."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1634\/theoncologist.2014-0305","article-title":"A phase II study of ifosfamide, methotrexate, etoposide, and prednisolone for previously untreated stage I\/II extranodal natural killer\/T-cell lymphoma, nasal type: A multicenter trial of the Korean Cancer Study Group","volume":"19","author":"Kim","year":"2014","journal-title":"Oncologist"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"4410","DOI":"10.1200\/JCO.2011.35.6287","article-title":"Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)\/T-cell lymphoma, nasal type: The NK-Cell Tumor Study Group study","volume":"29","author":"Yamaguchi","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1182\/blood-2010-09-307454","article-title":"Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK\/T-cell lymphoma, a phase 2 study","volume":"117","author":"Jaccard","year":"2011","journal-title":"Blood"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.1182\/blood-2017-12-791418","article-title":"Advances in the treatment of extranodal NK\/T-cell lymphoma, nasal type","volume":"131","author":"Yamaguchi","year":"2018","journal-title":"Blood"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1016\/j.bbmt.2017.07.027","article-title":"Clinical practice recommendations on indication and timing of hematopoietic cell transplantation in mature T CELL and NK\/T cell lymphomas: An International collaborative effort on behalf of the guidelines committee of the American Society for Blood and Marrow Transplantation","volume":"23","author":"Kumar","year":"2017","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"5594","DOI":"10.1200\/JCO.2009.23.8295","article-title":"Phase I\/II study of concurrent chemoradiotherapy for localized nasal natural killer\/T-cell lymphoma: Japan Clinical Oncology Group study JCOG0211","volume":"27","author":"Yamaguchi","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_120","first-page":"85","article-title":"nasal NK\/T-cell lymphoma","volume":"58","author":"Takahara","year":"2019","journal-title":"Jpn. J. Rhinool."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/S1470-2045(18)30379-6","article-title":"Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): An international, open-label, randomised, controlled phase 3 trial","volume":"19","author":"Kim","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s00262-017-1987-x","article-title":"Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer\/T-cell lymphoma: A potential rationale for immunotherapy","volume":"66","author":"Nagato","year":"2017","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1182\/blood-2016-12-756841","article-title":"PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK\/T-cell lymphoma failing l-asparaginase","volume":"129","author":"Kwong","year":"2017","journal-title":"Blood"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"3658","DOI":"10.1158\/1078-0432.CCR-03-0640","article-title":"Identification of C-met oncogene as a broadly expressed tumor-associated antigen recognized by cytotoxic T-lymphocytes","volume":"10","author":"Schag","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1158\/1078-0432.CCR-12-2522","article-title":"Effective anti-neu-initiated antitumor responses require the complex role of CD4+ T cells","volume":"19","author":"Mortenson","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coi.2016.11.001","article-title":"Peptide vaccines in cancer-old concept revisited","volume":"45","author":"Kumai","year":"2017","journal-title":"Curr. Opin. Immunol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1002\/eji.200535485","article-title":"Epstein-Barr virus (EBV) latent membrane protein-1-specific cytotoxic T lymphocytes targeting EBV-carrying natural killer cell malignancies","volume":"36","author":"Ito","year":"2006","journal-title":"Eur. J. Immunol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1158\/0008-5472.CAN-07-3212","article-title":"Induction of EBV-latent membrane protein 1-specific MHC class II-restricted T-cell responses against natural killer lymphoma cells","volume":"68","author":"Kobayashi","year":"2008","journal-title":"Cancer Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"3695","DOI":"10.1182\/blood-2010-06-292268","article-title":"A novel latent membrane 2 transcript expressed in Epstein-Barr virus-positive NK- and T-cell lymphoproliferative disease encodes a target for cellular immunotherapy","volume":"116","author":"Fox","year":"2010","journal-title":"Blood"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/7\/1381\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:23:57Z","timestamp":1760163837000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/7\/1381"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,25]]},"references-count":129,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["microorganisms9071381"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms9071381","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,25]]}}}