{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T05:18:11Z","timestamp":1763183891655,"version":"3.45.0"},"reference-count":63,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematology Reports"],"abstract":"<jats:p>Background\/Objectives: In children developing B-cell acute lymphoblastic leukemia (B-ALL), an immune evasion event takes place where otherwise \u201csilent\u201d preleukemic cells undergo a malignant transformation while escaping immune control, often through unknown mechanisms. Methods and Results: Here, we identify the upregulation of PD-1 expression in preleukemic cells, triggered by Pax5 inactivation in mice and correlating with the time of conversion to leukemia, as a novel marker that favors leukemia evasion. This increase in PD-1 expression is apparent across diverse molecular B-ALL subtypes, both in mice and humans. PD-1 is not required for B-cell leukemogenesis, but, in the absence of PD-1, tumor cells express NK cell inhibitory receptors, highlighting the necessity for leukemic cells to evade the host\u2019s NK immune response in order to exit the bone marrow. PD-1 expression reduces natural antitumor immune responses, but it sensitizes leukemic cells to immune checkpoint blockade strategies in mice and humans. PD-1 targeting confers clinical benefits by restoring NK-mediated tumor cell killing in vitro and eliminating tumor cells in vivo in mice engrafted with B-ALL. Conclusions: These results identify PD-1 as a new therapeutic target against leukemic progression, providing new opportunities for the treatment and possibly also the prevention of childhood B-ALL.<\/jats:p>","DOI":"10.3390\/hematolrep17060061","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T11:49:43Z","timestamp":1763120983000},"page":"61","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PD-1 Expression Promotes Immune Evasion in B-ALL"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1510-1499","authenticated-orcid":false,"given":"Ana","family":"Casado-Garc\u00eda","sequence":"first","affiliation":[{"name":"Experimental Therapeutics and Translational Oncology Program, Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer, CSIC-USAL, Campus M. de Unamuno s\/n, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno s\/n, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gonzalo","family":"Garc\u00eda-Aguilera","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital Universitario La Princesa, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julio","family":"Pozo","sequence":"additional","affiliation":[{"name":"Servicio de Citometr\u00eda, Departamento de Medicina, Biomedical Research Networking Centre on Cancer CIBER-CIBERONC (CB16\/12\/00400), Institute of Health Carlos III, and Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer (CIC-IBMCC), CSIC\/Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9806-0217","authenticated-orcid":false,"given":"Ninad","family":"Oak","sequence":"additional","affiliation":[{"name":"Department of Oncology, St. Jude Children\u2019s Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana","family":"Barrena","sequence":"additional","affiliation":[{"name":"Servicio de Citometr\u00eda, Departamento de Medicina, Biomedical Research Networking Centre on Cancer CIBER-CIBERONC (CB16\/12\/00400), Institute of Health Carlos III, and Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer (CIC-IBMCC), CSIC\/Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bel\u00e9n","family":"Ruiz-Corzo","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics and Translational Oncology Program, Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer, CSIC-USAL, Campus M. de Unamuno s\/n, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno s\/n, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2362-8323","authenticated-orcid":false,"given":"Jaanam","family":"Lalchandani","sequence":"additional","affiliation":[{"name":"Advance Therapy Unit, Oncohematology Department, Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital Infantil Universitario del Ni\u00f1o Jes\u00fas, Avenida Menendez y Pelayo, 65 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Chamorro-Vera","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Universidad Aut\u00f3noma de Madrid, Avenida Menendez y Pelayo, 65, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Castillo-Robleda","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Universidad Aut\u00f3noma de Madrid, Avenida Menendez y Pelayo, 65, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Soriano","sequence":"additional","affiliation":[{"name":"Servicio de Citometr\u00eda, Departamento de Medicina, Biomedical Research Networking Centre on Cancer CIBER-CIBERONC (CB16\/12\/00400), Institute of Health Carlos III, and Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer (CIC-IBMCC), CSIC\/Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9655-2242","authenticated-orcid":false,"given":"Silvia","family":"Alem\u00e1n-Arteaga","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics and Translational Oncology Program, Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer, CSIC-USAL, Campus M. de Unamuno s\/n, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno s\/n, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena G.","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Advance Therapy Unit, Oncohematology Department, Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital Infantil Universitario del Ni\u00f1o Jes\u00fas, Avenida Menendez y Pelayo, 65 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6809-5489","authenticated-orcid":false,"given":"Jorge","family":"Mart\u00ednez-Cano","sequence":"additional","affiliation":[{"name":"Immune System Development and Function Unit, Centro de Biolog\u00eda Molecular Severo Ochoa (Consejo Superior de Investigaciones Cient\u00edficas-Universidad Aut\u00f3noma de Madrid), 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0430-312X","authenticated-orcid":false,"given":"Andrea","family":"L\u00f3pez-\u00c1lvarez de Neyra","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics and Translational Oncology Program, Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer, CSIC-USAL, Campus M. de Unamuno s\/n, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno s\/n, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Somoza-Cotillas","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics and Translational Oncology Program, Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer, CSIC-USAL, Campus M. de Unamuno s\/n, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno s\/n, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar","family":"Blanco","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno s\/n, 37007 Salamanca, Spain"},{"name":"Departamento de Anatom\u00eda Patol\u00f3gica, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana","family":"Riesco","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno s\/n, 37007 Salamanca, Spain"},{"name":"Department of Pediatrics, Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2680-3285","authenticated-orcid":false,"given":"Pablo","family":"Prieto-Matos","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno s\/n, 37007 Salamanca, Spain"},{"name":"Department of Pediatrics, Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco Javier","family":"Garc\u00eda Criado","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno s\/n, 37007 Salamanca, Spain"},{"name":"Departamento de Cirug\u00eda, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8950-8542","authenticated-orcid":false,"given":"Mar\u00eda Bego\u00f1a","family":"Garc\u00eda Cenador","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno s\/n, 37007 Salamanca, Spain"},{"name":"Departamento de Cirug\u00eda, Universidad de Salamanca, 37007 Salamanca, 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Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5581-6555","authenticated-orcid":false,"given":"Kim E","family":"Nichols","sequence":"additional","affiliation":[{"name":"Department of Oncology, St. Jude Children\u2019s Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-7230","authenticated-orcid":false,"given":"Alberto","family":"Orfao","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno s\/n, 37007 Salamanca, Spain"},{"name":"Servicio de Citometr\u00eda, Departamento de Medicina, Biomedical Research Networking Centre on Cancer CIBER-CIBERONC (CB16\/12\/00400), Institute of Health Carlos III, and Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer (CIC-IBMCC), CSIC\/Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0332-6973","authenticated-orcid":false,"given":"Manuel","family":"Ram\u00edrez-Orellana","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Universidad Aut\u00f3noma de Madrid, Avenida Menendez y Pelayo, 65, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6989-9905","authenticated-orcid":false,"given":"Isidro","family":"S\u00e1nchez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics and Translational Oncology Program, Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer, CSIC-USAL, Campus M. de Unamuno s\/n, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno s\/n, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/nature05690","article-title":"Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia","volume":"446","author":"Mullighan","year":"2007","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nature25480","article-title":"The landscape of genomic alterations across childhood cancers","volume":"555","author":"Grobner","year":"2018","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/ng.2532","article-title":"The genomic landscape of hypodiploid acute lymphoblastic leukemia","volume":"45","author":"Holmfeldt","year":"2013","journal-title":"Nat. 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