{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T17:22:45Z","timestamp":1794504165641,"version":"4.9.1"},"reference-count":66,"publisher":"American Society of Hematology","issue":"20","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,11,12]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Although first-line immunotherapy achieves remission in most patients with follicular lymphoma (FL), improved biomarkers and therapeutic strategies are required to identify and manage those who relapse. We investigated the immune microenvironment at diagnosis in uniformly treated patients with FL with extended follow-up (&amp;gt;11 years), comparing patients with relapsed disease and those with relapse-free disease. Transcriptomic profiling revealed the enrichment of inflammatory response pathways in relapsed patients, including cytokine overexpression and upregulation of CD70, a molecule implicated in immune activation and inflammation. Multiplex immunofluorescence confirmed CD70 overexpression at diagnosis in tumor cells as well as in CD8+ and CD4+ T follicular helper cells, correlating with inferior progression-free survival. Functional studies demonstrated that CD70+ tumor cells were more proliferative and induced CD70 expression in T cells, suggesting a feed-forward loop sustaining immune activation. To target these cells and enhance current chimeric antigen receptor (CAR) T-cell approaches, we engineered dual CD19-CD70 CAR T cells by cotransducing the CD19 CAR T-cell product ARI-0001 with a CD27-based anti-CD70 CAR. Dual CAR T cells exhibited enhanced in vitro cytotoxicity against patient-derived spheroids of FL, diffuse large B-cell lymphoma, and mantle cell lymphoma. In FL xenograft models, dual CAR T-cell treatment achieved superior disease control compared to monotargeted CAR T cells, inducing complete tumor clearance in the spleen and bone marrow. Collectively, these findings provide a strong preclinical rationale for the clinical development of CD19-CD70 dual CAR T-cell therapy to improve outcomes in high-risk FL and potentially other B-cell non-Hodgkin lymphomas.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025032663","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T21:54:47Z","timestamp":1784757287000},"page":"2511-2527","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":1,"title":["CD70 overexpression at diagnosis predicts relapse and supports dual CD19-CD70 CAR T-cell therapy in follicular lymphoma"],"prefix":"10.1182","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7288-7737","authenticated-orcid":false,"given":"Ferran","family":"Araujo-Ayala","sequence":"first","affiliation":[{"name":"1Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2013Institut d'Investigacions Biom\u00e8diques August Pi Sunyer, Barcelona, Spain"},{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red-Oncolog\u00eda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4532-9866","authenticated-orcid":false,"given":"Maria","family":"Ros","sequence":"additional","affiliation":[{"name":"1Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2013Institut d'Investigacions Biom\u00e8diques August Pi Sunyer, Barcelona, Spain"},{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red-Oncolog\u00eda, Madrid, Spain"},{"name":"3Biomedicine Program, University of Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1903-5636","authenticated-orcid":false,"given":"Raluca","family":"Alexandru","sequence":"additional","affiliation":[{"name":"4Department of Pathology, Cl\u00ednica Universidad de Navarra, Pamplona, 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