{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:16:12Z","timestamp":1790266572317,"version":"4.1.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universit\u00e0 del Sannio"},{"name":"Fondazione Buzzi"},{"DOI":"10.13039\/501100005010","name":"Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG 2018\u2010ID21763"],"award-info":[{"award-number":["IG 2018\u2010ID21763"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG2020\u2010ID27702"],"award-info":[{"award-number":["IG2020\u2010ID27702"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG2019\u2010ID24290"],"award-info":[{"award-number":["IG2019\u2010ID24290"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Mol Med"],"published-print":{"date-parts":[[2021,6,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Boosting antitumor immunity has emerged as a powerful strategy in cancer treatment. While releasing T\u2010cell brakes has received most attention, tumor recognition by T cells is a pre\u2010requisite. Radiotherapy and certain cytotoxic drugs induce the release of damage\u2010associated molecular patterns, which promote tumor antigen cross\u2010presentation and T\u2010cell priming. Antibodies against the \u201cdo not eat me\u201d signal CD47 cause macrophage phagocytosis of live tumor cells and drive the emergence of antitumor T cells. Here we show that CXCR4 activation, so far associated only with tumor progression and metastasis, also flags tumor cells to immune recognition. Both CXCL12, the natural CXCR4 ligand, and BoxA, a fragment of HMGB1, promote the release of DAMPs and the internalization of CD47, leading to protective antitumor immunity. We designate as Immunogenic Surrender the process by which CXCR4 turns in tumor cells to macrophages, thereby subjecting a rapidly growing tissue to immunological scrutiny. Importantly, while CXCL12 promotes tumor cell proliferation, BoxA reduces it, and might be exploited for the treatment of malignant mesothelioma and a variety of other tumors.<\/jats:p>","DOI":"10.15252\/emmm.202012344","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T13:30:08Z","timestamp":1620394208000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["CXCR4 engagement triggers CD47 internalization and antitumor immunization in a mouse model of mesothelioma"],"prefix":"10.1038","volume":"13","author":[{"given":"Rosanna","family":"Mezzapelle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1275-5470","authenticated-orcid":false,"given":"Francesco","family":"De Marchis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Passera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Leo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Brambilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Colombo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"Casalgrandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Preti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Zambrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6326-5853","authenticated-orcid":false,"given":"Patrizia","family":"Castellani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Ertassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Silingardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Caprioglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Basso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzo","family":"Boldorini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Carretta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Sanvito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ottavio","family":"Rena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rubartelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Sabatino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Mondino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo P","family":"Crippa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Colantuoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco E","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,6]]},"reference":[{"key":"BFEMMM202012344_CR2","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1038\/nm1622","volume":"13","author":"L Apetoh","year":"2007","unstructured":"Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, Mignot G, Maiuri MC, Ullrich E, Saulnier P et al (2007) Toll\u2010like receptor 4\u2010dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 13: 1050\u20131059","journal-title":"Nat Med"},{"key":"BFEMMM202012344_CR3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1146\/annurev-immunol-032713-120142","volume":"32","author":"AN Barclay","year":"2014","unstructured":"Barclay AN, van den Berg TK (2014) The interaction between signal regulatory protein alpha (SIRP\u03b1) and CD47: structure, function, and therapeutic target. Annu Rev Immunol 32: 25\u201350","journal-title":"Annu Rev Immunol"},{"key":"BFEMMM202012344_CR4","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1038\/s41418-017-0044-9","volume":"25","author":"L Bezu","year":"2018","unstructured":"Bezu L, Sauvat A, Humeau J, Gomes\u2010da\u2010Silva LC, Iribarren K, Forveille S, Garcia P, Zhao L, Liu P, Zitvogel L et al (2018) eIF2\u03b1 phosphorylation is pathognomonic for immunogenic cell death. Cell Death Differ 25: 1375\u20131393","journal-title":"Cell Death Differ"},{"key":"BFEMMM202012344_CR5","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/imr.12601","volume":"280","author":"ME Bianchi","year":"2017","unstructured":"Bianchi ME, Crippa MP, Manfredi AA, Mezzapelle R, Rovere Querini P, Venereau E (2017) High\u2010mobility group box 1 protein orchestrates responses to tissue damage via inflammation, innate and adaptive immunity, and tissue repair. Immunol Rev 280: 74\u201382","journal-title":"Immunol Rev"},{"key":"BFEMMM202012344_CR6","first-page":"1","volume":"11","author":"ME Bianchi","year":"2020","unstructured":"Bianchi ME, Mezzapelle R (2020) The chemokine receptor CXCR4 in cell proliferation and tissue regeneration. Front Immunol 11: 1\u20138","journal-title":"Front Immunol"},{"key":"BFEMMM202012344_CR7","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1084\/jem.194.4.541","volume":"194","author":"BR Blazar","year":"2001","unstructured":"Blazar BR, Lindberg FP, Ingulli E, Panoskaltsis\u2010Mortari A, Oldenborg P\u2010A, Iizuka K, Yokoyama WM, Taylor PA (2001) CD47 (integrin\u2010associated protein) engagement of dendritic cell and macrophage counterreceptors is required to prevent the clearance of donor lymphohematopoietic cells. J Exp Med 194: 541\u2013550","journal-title":"J Exp Med"},{"key":"BFEMMM202012344_CR8","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1158\/0008-5472.CAN-10-2238","volume":"71","author":"MP Chao","year":"2011","unstructured":"Chao MP, Alizadeh AA, Tang C, Jan M, Weissman\u2010tsukamoto R, Zhao F, Park CY, Weissman IL, Majeti R (2011) Therapeutic antibody targeting of CD47 eliminates human acute lymphoblastic leukemia. Cancer Res 71: 1374\u20131385","journal-title":"Cancer Res"},{"key":"BFEMMM202012344_CR9","first-page":"63ra94","volume":"2","author":"MP Chao","year":"2010","unstructured":"Chao MP, Jaiswal S, Weissman\u2010Tsukamoto R, Alizadeh AA, Gentles AJ, Volkmer J, Weiskopf K, Willingham SB, Raveh T, Park CY et al (2010) Calreticulin is the dominant pro\u2010phagocytic signal on multiple human cancers and is counterbalanced by CD47. Sci Transl Med. 2: 63ra94","journal-title":"Sci Transl Med."},{"key":"BFEMMM202012344_CR11","volume":"3","author":"L Galluzzi","year":"2020","unstructured":"Galluzzi L, Vitale I, Warren S, Adjemian S, Agostinis P, Martinez AB, Chan TA, Coukos G, Demaria S, Deutsch E et al (2020) Consensus guidelines for the definition, detection and interpretation of immunogenic cell death. J Immunother Cancer 3: e955691","journal-title":"J Immunother Cancer"},{"key":"BFEMMM202012344_CR12","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/onc.2015.139","volume":"35","author":"F Guo","year":"2016","unstructured":"Guo F, Wang Y, Liu J, Mok SC, Xue F, Zhang W (2016) CXCL12\/CXCR4: a symbiotic bridge linking cancer cells and their stromal neighbors in oncogenic communication networks. Oncogene 35: 816\u2013826","journal-title":"Oncogene"},{"key":"BFEMMM202012344_CR13","first-page":"1","volume":"24","author":"M He","year":"2018","unstructured":"He M, Bianchi ME, Coleman TR, Tracey KJ, Al\u2010Abed Y (2018) Exploring the biological functional mechanism of the HMGB1\/TLR4\/MD\u20102 complex by surface plasmon resonance. Mol Med 24: 1\u20139","journal-title":"Mol Med"},{"key":"BFEMMM202012344_CR14","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1126\/scisignal.aat2214","volume":"11","author":"B Hitchinson","year":"2017","unstructured":"Hitchinson B, Eby JM, Gao X, Guite\u2010Vinet F, Ziarek JJ, Abdelkarim H, Lee Y, Okamoto Y, Shikano S, Majetschak M et al (2017) Biased antagonism of CXCR4 avoids antagonist tolerance. Sci Signal 11: 2214","journal-title":"Sci Signal"},{"key":"BFEMMM202012344_CR15","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2009.05.046","volume":"138","author":"S Jaiswal","year":"2009","unstructured":"Jaiswal S, Jamieson CHM, Pang WW, Park CY, Chao MP, Majeti R, Traver D, Van RN, Weissman IL (2009) CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell 138: 271\u2013285","journal-title":"Cell"},{"key":"BFEMMM202012344_CR16","doi-asserted-by":"crossref","first-page":"3290","DOI":"10.1158\/0008-5472.CAN-11-3481","volume":"72","author":"S Jube","year":"2012","unstructured":"Jube S, Rivera ZS, Bianchi ME, Powers A, Wang E, Pagano I, Pass HI, Gaudino G, Carbone M, Yang H (2012) Cancer cell secretion of the DAMP protein HMGB1 supports progression in malignant mesothelioma. Cancer Res 72: 3290\u20133301","journal-title":"Cancer Res"},{"key":"BFEMMM202012344_CR17","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev-immunol-032712-100008","volume":"31","author":"G Kroemer","year":"2012","unstructured":"Kroemer G, Galluzzi L, Kepp O, Zitvogel L (2012) Immunogenic cell death in cancer therapy. Annu Rev Immunol 31: 51\u201372","journal-title":"Annu Rev Immunol"},{"key":"BFEMMM202012344_CR18","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/path.2829","volume":"223","author":"T Li","year":"2011","unstructured":"Li T, Li H, Wang Y, Harvard C, Tan JL, Au A, Xu Z, Jablons DM, You L (2011) The expression of CXCR4, CXCL12 and CXCR7 in malignant pleural mesothelioma. J Pathol 223: 519\u2013530","journal-title":"J Pathol"},{"key":"BFEMMM202012344_CR19","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.lungcan.2013.02.017","volume":"80","author":"LA Lievense","year":"2013","unstructured":"Lievense LA, Bezemer K, Aerts JGJV, Hegmans JPJJ (2013) Tumor\u2010associated macrophages in thoracic malignancies. Lung Cancer 80: 256\u2013262","journal-title":"Lung Cancer"},{"key":"BFEMMM202012344_CR20","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/gt.2008.177","volume":"16","author":"MP Limberis","year":"2009","unstructured":"Limberis MP, Bell CL, Wilson JM (2009) Identification of the murine firefly luciferase\u2010specific CD8 T\u2010cell epitopes. Gene Ther 16: 441\u2013447","journal-title":"Gene Ther"},{"key":"BFEMMM202012344_CR21","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1038\/nm.3931","volume":"21","author":"X Liu","year":"2015","unstructured":"Liu X, Cron K, Xu MM, Fu Y\u2010X, Pu Y, Peng H, Xu H, Deng L, Kline J, Frazier WA (2015) CD47 blockade triggers T cell\u2013mediated destruction of immunogenic tumors. Nat Med 21: 1209\u20131215","journal-title":"Nat Med"},{"key":"BFEMMM202012344_CR22","doi-asserted-by":"crossref","first-page":"22850","DOI":"10.1038\/srep22850","volume":"6","author":"R Mezzapelle","year":"2016","unstructured":"Mezzapelle R, Rrapaj E, Gatti E, Ceriotti C, Marchis FD, Preti A, Spinelli AE, Perani L, Venturini M, Valtorta S et al (2016) Human malignant mesothelioma is recapitulated in immunocompetent BALB\/c mice injected with murine AB cells. Sci Rep 6: 22850","journal-title":"Sci Rep"},{"key":"BFEMMM202012344_CR23","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/emboj.2009.1","volume":"28","author":"T Panaretakis","year":"2009","unstructured":"Panaretakis T, Kepp O, Brockmeier U, Tesniere A, Bjorklund A\u2010C, Chapman DC, Durchschlag M, Joza N, Pierron G, van Endert P et al (2009) Mechanisms of pre\u2010apoptotic calreticulin exposure in immunogenic cell death. EMBO J 28: 578\u2013590","journal-title":"EMBO J"},{"key":"BFEMMM202012344_CR24","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1038\/sj.embor.7400205","volume":"5","author":"P Rovere\u2010Querini","year":"2004","unstructured":"Rovere\u2010Querini P, Capobianco A, Scaffidi P, Valentinis B, Catalanotti F, Giazzon M, Dumitriu IE, M\u00fcller S, Iannacone M, Traversari C et al (2004) HMGB1 is an endogenous immune adjuvant released by necrotic cells. EMBO Rep 5: 825\u2013830","journal-title":"EMBO Rep"},{"key":"BFEMMM202012344_CR25","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1038\/nmeth947","volume":"3","author":"O S\u00f6derberg","year":"2006","unstructured":"S\u00f6derberg O, Gullberg M, Jarvius M, Ridderstr\u00e5le K, Leuchowius K\u2010J, Jarvius J, Wester K, Hydbring P, Bahram F, Larsson L\u2010G et al (2006) Direct observation of individual endogenous protein complexes in situ by proximity ligation. Nat Methods 3: 995\u20131000","journal-title":"Nat Methods"},{"key":"BFEMMM202012344_CR26","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1158\/1078-0432.CCR-09-2329","volume":"16","author":"BA Teicher","year":"2010","unstructured":"Teicher BA, Fricker SP (2010) CXCL12 (SDF\u20101)\/CXCR4 pathway in cancer. Clin Cancer Res 16: 2927\u20132931","journal-title":"Clin Cancer Res"},{"key":"BFEMMM202012344_CR27","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1053\/j.gastro.2010.01.058","volume":"138","author":"J Terzi\u0107","year":"2010","unstructured":"Terzi\u0107 J, Grivennikov S, Karin E, Karin M (2010) Inflammation and colon cancer. Gastroenterology 138: 2101\u20132114","journal-title":"Gastroenterology"},{"key":"BFEMMM202012344_CR28","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1084\/jem.20160217","volume":"215","author":"M Tirone","year":"2018","unstructured":"Tirone M, Tran NL, Ceriotti C, Gorzanelli A, Canepari M, Bottinelli R, Raucci A, Di Maggio S, Santiago C, Mellado M et al (2018) High mobility group box 1 orchestrates tissue regeneration via CXCR4. J Exp Med 215: 303\u2013318","journal-title":"J Exp Med"},{"key":"BFEMMM202012344_CR29","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.phrs.2016.06.031","volume":"111","author":"E Venereau","year":"2016","unstructured":"Venereau E, De Leo F, Mezzapelle R, Careccia G, Musco G, Bianchi ME (2016) HMGB1 as biomarker and drug target. Pharmacol Res 111: 534\u2013544","journal-title":"Pharmacol Res"},{"key":"BFEMMM202012344_CR30","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.tips.2014.04.007","volume":"35","author":"JD Violin","year":"2014","unstructured":"Violin JD, Crombie AL, Soergel DG, Lark MW (2014) Biased ligands at G\u2010protein\u2010coupled receptors: promise and progress. Trends Pharmacol Sci 35: 308\u2013316","journal-title":"Trends Pharmacol Sci"},{"key":"BFEMMM202012344_CR31","doi-asserted-by":"crossref","first-page":"6662","DOI":"10.1073\/pnas.1121623109","volume":"109","author":"SB Willingham","year":"2012","unstructured":"Willingham SB, Volkmer J\u2010P, Gentles AJ, Sahoo D, Dalerba P, Mitra SS, Wang J, Contreras\u2010Trujillo H, Martin R, Cohen JD et al (2012) The CD47\u2010signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc Natl Acad Sci USA 109: 6662\u20136667","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMMM202012344_CR32","first-page":"1","volume":"9","author":"J Xue","year":"2020","unstructured":"Xue J, Patergnani S, Giorgi C, Suarez J, Goto K, Bononi A, Tanji M, Novelli F, Pastorino S, Xu R et al (2020) Asbestos induces mesothelial cell transformation via HMGB1\u2010induced authophagy. Proc Natl Acad Sci USA 9: 1\u201310","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMMM202012344_CR33","volume":"6","author":"H Yang","year":"2015","unstructured":"Yang H, Pellegrini L, Napolitano A, Giorgi C, Jube S, Preti A, Jennings CJ, De Marchis F, Flores EG, Larson D et al (2015) Aspirin delays mesothelioma growth by inhibiting HMGB1\u2010mediated tumor progression. Cell Death Dis 6: e1786","journal-title":"Cell Death Dis"},{"key":"BFEMMM202012344_CR34","doi-asserted-by":"crossref","first-page":"12611","DOI":"10.1073\/pnas.1006542107","volume":"107","author":"H Yang","year":"2010","unstructured":"Yang H, Rivera Z, Jube S, Nasu M, Bertino P, Goparaju C, Franzoso G, Lotze MT, Krausz T, Pass HI et al (2010) Programmed necrosis induced by asbestos in human mesothelial cells causes high\u2010mobility group box 1 protein release and resultant inflammation. Proc Natl Acad Sci USA 107: 12611\u201312616","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["EMBO Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.202012344.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/emmm.202012344","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/emmm.202012344\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/emmm.202012344","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.202012344.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:30:39Z","timestamp":1779085839000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/emmm.202012344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,6]]},"references-count":32,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6,8]]}},"alternative-id":["BFEMMM202012344"],"URL":"https:\/\/doi.org\/10.15252\/emmm.202012344","relation":{},"ISSN":["1757-4676","1757-4684"],"issn-type":[{"value":"1757-4676","type":"print"},{"value":"1757-4684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,6]]},"assertion":[{"value":"14 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"MEB is founder and part owner of HMGBiotech, and MC and AP were partially supported by HMGBiotech. The other authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"EMMM202012344"}}