{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T06:12:49Z","timestamp":1770271969489,"version":"3.49.0"},"reference-count":76,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":306,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004097","name":"Fondation ARC pour la Recherche sur le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018737","name":"Laboratoire d'Excellence Inflamex","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp;amp; Trans Imm"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Diffuse large B\u2010cell lymphoma (DLBCL) constitutes 30\u201340% of non\u2010Hodgkin lymphoma cases. Despite therapeutic advances, persistence of relapsed cases has been linked to the complex tumor microenvironment (TME) and its interactions with lymphoma cells. In particular, characterising T\u2010cell subsets, including rare cell types, and their interplay with the remaining TME is crucial for unravelling DLBCL pathogenesis and refining therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using flow and spectral cytometry with unsupervised analysis, we investigated T\u2010cell subpopulations across DLBCL biopsies and control lymph nodes (LN). We also inferred communication pathways between T\u00a0cells and other immune cells in the TME based on the correlation of ligand\u2013receptor expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our analysis revealed a higher frequency of CD8\n                      <jats:sup>+<\/jats:sup>\n                      follicular regulatory T (Tfr) cells in DLBCL biopsies compared to control LN. These cells exhibited an effector\u2010memory phenotype (CD45RA\n                      <jats:sup>\u2212<\/jats:sup>\n                      CCR7\n                      <jats:sup>\u2212<\/jats:sup>\n                      ), expressed follicular markers (PD\u20101\n                      <jats:sup>+<\/jats:sup>\n                      CXCR5\n                      <jats:sup>+<\/jats:sup>\n                      ) and had a regulatory profile (CD127\n                      <jats:sup>\u2212<\/jats:sup>\n                      CD25\n                      <jats:sup>+<\/jats:sup>\n                      ) along with an activation\/co\u2010stimulatory signature (HLA\u2010DR\n                      <jats:sup>+<\/jats:sup>\n                      , ICOS\n                      <jats:sup>+<\/jats:sup>\n                      , CD95\n                      <jats:sup>+<\/jats:sup>\n                      ). Correlation analysis highlighted a co\u2010stimulatory interaction between lymphoma B cells and CD8\n                      <jats:sup>+<\/jats:sup>\n                      Tfr cells through the ICOS\/ICOSL pathway, which may contribute to a protumor effect. Validation in independent scRNAseq and flow cytometry datasets confirmed the notable prevalence of CD8\n                      <jats:sup>+<\/jats:sup>\n                      Tfr cells in DLBCL biopsies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study highlights the utility of high\u2010dimensional computational cytometry in elucidating T\u2010cell subpopulations, including an increased frequency of CD8\n                      <jats:sup>+<\/jats:sup>\n                      follicular regulatory T\u00a0cells and their communication patterns within the DLBCL TME. This unbiased approach sheds light on novel cellular mechanisms in DLBCL, uncovering potential targets and biomarkers for immunotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cti2.70062","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T20:21:39Z","timestamp":1762201299000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["High\u2010dimensional spectral cytometry identifies follicular regulatory CD8\n                    <sup>+<\/sup>\n                    T\u00a0cells in diffuse large B\u2010cell lymphoma"],"prefix":"10.1002","volume":"14","author":[{"given":"Alba","family":"D\u00edaz Herrero","sequence":"first","affiliation":[{"name":"Institut de Recherche Saint\u2010Louis Universit\u00e9 Paris\u2010Cit\u00e9, Inserm U1342  Paris 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