{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:18:57Z","timestamp":1785403137104,"version":"3.56.0"},"reference-count":55,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PMP21\/00015 (PREGENLINF)"],"award-info":[{"award-number":["PMP21\/00015 (PREGENLINF)"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PMP21\/00015 (PREGENLINF)"],"award-info":[{"award-number":["PMP21\/00015 (PREGENLINF)"]}],"id":[{"id":"https:\/\/ror.org\/00ca2c886","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014139","name":"CIBERONC","doi-asserted-by":"publisher","award":["CB16\/12\/00489"],"award-info":[{"award-number":["CB16\/12\/00489"]}],"id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"award":["CB16\/12\/00489"],"award-info":[{"award-number":["CB16\/12\/00489"]}],"id":[{"id":"https:\/\/ror.org\/04hya7017","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Gobierno de Navarra Department of Economic Development","award":["0011-1411-2022-000068"],"award-info":[{"award-number":["0011-1411-2022-000068"]}]},{"name":"Gobierno de Navarra Department of Economic Development","award":["0011-1411-2022-000077"],"award-info":[{"award-number":["0011-1411-2022-000077"]}]},{"name":"Gobierno de Navarra Department of Economic Development","award":["0011-1411-2023-000074"],"award-info":[{"award-number":["0011-1411-2023-000074"]}]},{"name":"Gobierno de Navarra Department of Economic Development","award":["0011-1411-2023-000105"],"award-info":[{"award-number":["0011-1411-2023-000105"]}]},{"name":"FC AECC"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) exhibit substantial heterogeneity, reflecting the diversity of the germinal center (GC). Histologic transformation of FL to DLBCL is associated with poor prognosis, yet robust biomarkers predicting transformation remain limited. Methods: We integrated single-cell DNA sequencing, single-cell RNA sequencing, and spatial transcriptomics in diagnostic lymph-node biopsies from non-transformed FL (ntFL), transformed FL (tFL), and DLBCL to characterize clonal states and immune niches in GC lymphomas. T-cell signatures associated with transformation were evaluated in an independently published single-cell FL dataset. Results: Transcriptional profiling revealed similarities between tFL and DLBCL, consistent with a GC-related malignant program. The tFL microenvironment showed enrichment of exhausted CD4+ regulatory and CD8+ effector T cells, together with CD4+ follicular helper T cells (Tfh) displaying an adhesion-related phenotype. Spatial analysis suggested increased proximity of exhausted\/immunosuppressive T cells and enhanced Tfh-B-cell interactions in tFL compared with ntFL. These immune signatures were also observed in an external cohort and were associated with early transformation. In addition, clonal hematopoiesis-associated mutations were detected in microenvironmental cells across samples, suggesting a potential contribution to the lymphoma microenvironment. Conclusions: This work demonstrates the feasibility of integrating single-cell and spatial analyses in GC lymphomas and provides a framework for investigating tumor heterogeneity and immune organization. These findings may inform future studies on biomarker development and the rational design of immunotherapies.<\/jats:p>","DOI":"10.3390\/cancers18071122","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T13:23:17Z","timestamp":1774963397000},"page":"1122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated Single-Cell and Spatial Multi-Omics of Clonal Precursors and Immune Niches in Germinal Center Lymphomas"],"prefix":"10.3390","volume":"18","author":[{"given":"Sof\u00eda","family":"Huerga-Dom\u00ednguez","sequence":"first","affiliation":[{"name":"Hematology and Cell Therapy Service, Cancer Center Cl\u00ednica Universidad de Navarra (CCUN), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Be\u00f1at","family":"Ariceta","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"},{"name":"Hematology-Oncology Program, Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA), Cancer Center Cl\u00ednica Universidad de Navarra (CCUN), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Aguirre-Ruiz","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"},{"name":"Hematology-Oncology Program, Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA), Cancer Center Cl\u00ednica Universidad de Navarra (CCUN), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6550-2621","authenticated-orcid":false,"given":"Miguel","family":"Canales","sequence":"additional","affiliation":[{"name":"Hematology and Cell Therapy Service, Cancer Center Cl\u00ednica Universidad de Navarra (CCUN), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/nri2217","article-title":"Germinal centres: Role in B-cell physiology and malignancy","volume":"8","author":"Klein","year":"2008","journal-title":"Nat. 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