{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:27:12Z","timestamp":1777354032291,"version":"3.51.4"},"reference-count":24,"publisher":"American Society of Hematology","issue":"15","license":[{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,4,11]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Relapsed or refractory acute myeloid leukemia (AML) remains a major therapeutic challenge. We have recently developed a V\u03b41+ \u03b3\u03b4 T cell\u2013based product for adoptive immunotherapy, named Delta One T (DOT) cells, and demonstrated their cytolytic capacity to eliminate AML cell lines and primary blasts in\u00a0vitro and in\u00a0vivo. However, the molecular mechanisms responsible for the broad DOT-cell recognition of AML cells remain poorly understood. Here, we dissected the role of natural killer (NK) cell receptor ligands in AML cell recognition by DOT cells. Screening of multiple AML cell lines highlighted a strong upregulation of the DNAM-1 ligands, CD155\/pulmonary vascular resistance (PVR), CD112\/nectin-2, as well as the NKp30 ligand, B7-H6, in contrast with NKG2D ligands. CRISPR-mediated ablation revealed key nonredundant and synergistic contributions of PVR and B7-H6 but not nectin-2 to DOT-cell targeting of AML cells. We further demonstrate that PVR and B7-H6 are critical for the formation of robust immunological synapses between AML and DOT cells. Importantly, PVR but not B7-H6 expression in primary AML samples predicted their elimination by DOT cells. These data provide new mechanistic insight into tumor targeting by DOT cells and suggest that assessing PVR expression levels may be highly relevant to DOT cell\u2013based clinical trials.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2023022992","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T19:23:16Z","timestamp":1709580196000},"page":"1488-1495","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":30,"title":["CD155\/PVR determines acute myeloid leukemia targeting by Delta One T cells"],"prefix":"10.1182","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5157-0033","authenticated-orcid":false,"given":"Sofia","family":"Mensurado","sequence":"first","affiliation":[{"name":"1Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5046-4685","authenticated-orcid":false,"given":"Carolina","family":"Conde\u00e7o","sequence":"additional","affiliation":[{"name":"1Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4605-5325","authenticated-orcid":false,"given":"Diego","family":"S\u00e1nchez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"2Josep Carreras Leukaemia Research Institute, Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Spain"},{"name":"3Red Espa\u00f1ola de Terapias Avanzadas, Instituto de Salud Carlos III, Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RD21\/0017\/0029), Madrid, Spain"},{"name":"4Aragon Health Research Institute, Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III, Zaragoza, Spain"},{"name":"5Aragon I+D Foundation, Zaragoza, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9420-6058","authenticated-orcid":false,"given":"Sara","family":"Shirley","sequence":"additional","affiliation":[{"name":"1Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3199-2199","authenticated-orcid":false,"given":"Rui M. L.","family":"Coelho","sequence":"additional","affiliation":[{"name":"1Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8352-2194","authenticated-orcid":false,"given":"N\u00e9stor","family":"Tirado","sequence":"additional","affiliation":[{"name":"2Josep Carreras Leukaemia Research Institute, Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Spain"},{"name":"3Red Espa\u00f1ola de Terapias Avanzadas, Instituto de Salud Carlos III, Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RD21\/0017\/0029), Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1906-4701","authenticated-orcid":false,"given":"Meritxell","family":"Vinyoles","sequence":"additional","affiliation":[{"name":"2Josep Carreras Leukaemia Research Institute, Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Spain"},{"name":"3Red Espa\u00f1ola de Terapias Avanzadas, Instituto de Salud Carlos III, Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RD21\/0017\/0029), Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2448-8699","authenticated-orcid":false,"given":"Rafael","family":"Blanco-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"1Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7339-9994","authenticated-orcid":false,"given":"Leandro","family":"Barros","sequence":"additional","affiliation":[{"name":"1Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0249-9285","authenticated-orcid":false,"given":"Beatriz","family":"Galv\u00e3o","sequence":"additional","affiliation":[{"name":"1Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9230-9870","authenticated-orcid":false,"given":"No\u00e9lia","family":"Cust\u00f3dio","sequence":"additional","affiliation":[{"name":"1Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6993-2450","authenticated-orcid":false,"given":"Maria","family":"Gomes da Silva","sequence":"additional","affiliation":[{"name":"6Instituto Portugu\u00eas de Oncologia Francisco Gentil, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9372-1007","authenticated-orcid":false,"given":"Pablo","family":"Men\u00e9ndez","sequence":"additional","affiliation":[{"name":"2Josep Carreras Leukaemia Research Institute, Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Spain"},{"name":"3Red Espa\u00f1ola de Terapias Avanzadas, Instituto de Salud Carlos III, Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RD21\/0017\/0029), Madrid, Spain"},{"name":"7Centro de Investigaci\u00f3n Biom\u00e9dica en Red-Oncolog\u00eda, Instituto de Salud Carlos III, Barcelona, Spain"},{"name":"8Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats, Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4141-9302","authenticated-orcid":false,"given":"Bruno","family":"Silva-Santos","sequence":"additional","affiliation":[{"name":"1Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"}]}],"member":"234","reference":[{"issue":"2","key":"2024041115211853100_bib1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1182\/blood.2019001239","article-title":"How I treat acute myeloid leukemia in the era of new 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