{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T09:23:39Z","timestamp":1778923419532,"version":"3.51.4"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009794","name":"Breast Cancer Now","doi-asserted-by":"publisher","award":["2015NovPR638"],"award-info":[{"award-number":["2015NovPR638"]}],"id":[{"id":"10.13039\/100009794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011692","name":"Children's Cancer and Leukaemia Group","doi-asserted-by":"publisher","award":["CCLGA201906"],"award-info":[{"award-number":["CCLGA201906"]}],"id":[{"id":"10.13039\/100011692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["105104\/Z\/14\/Z"],"award-info":[{"award-number":["105104\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The spatial architecture of the lymphoid tissue in follicular lymphoma (FL) presents unique challenges to studying its immune microenvironment. We investigated the spatial interplay of T cells, macrophages, myeloid cells and natural killer T cells using multispectral immunofluorescence images of diagnostic biopsies of 32 patients. A deep learning\u2010based image analysis pipeline was tailored to the needs of follicular lymphoma spatial histology research, enabling the identification of different immune cells within and outside neoplastic follicles. We analyzed the density and spatial co\u2010localization of immune cells in the inter\u2010follicular and intra\u2010follicular regions of follicular lymphoma. Low inter\u2010follicular density of CD8+FOXP3+ cells and co\u2010localization of CD8+FOXP3+ with CD4+CD8+ cells were significantly associated with relapse (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0057 and\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0019, respectively) and shorter time to progression after first\u2010line treatment (Logrank\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0097 and log\u2010rank\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0093, respectively). A low inter\u2010follicular density of CD8+FOXP3+ cells is associated with increased risk of relapse independent of follicular lymphoma international prognostic index (FLIPI) (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.038, Hazard ratio (HR)\u00a0=\u00a00.42 [0.19, 0.95], but not independent of co\u2010localization of CD8+FOXP3+ with CD4+CD8+ cells (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.43). Co\u2010localization of CD8+FOXP3+ with CD4+CD8+ cells is predictors of time to relapse independent of the FLIPI score and density of CD8+FOXP3+ cells (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.027, HR\u00a0=\u00a00.0019 [7.19\u00a0\u00d7\u00a010\n                    <jats:sup>\u22126<\/jats:sup>\n                    , 0.49], This suggests a potential role of inter\u2010follicular CD8+FOXP3+ and CD4+CD8+ cells in the disease progression of FL, warranting further validation on larger patient cohorts.\n                  <\/jats:p>","DOI":"10.1002\/hon.3003","type":"journal-article","created":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T04:14:33Z","timestamp":1650600873000},"page":"541-553","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["High inter\u2010follicular spatial co\u2010localization of CD8+FOXP3+ with CD4+CD8+ cells predicts favorable outcome in follicular lymphoma"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0357-6297","authenticated-orcid":false,"given":"Yeman B.","family":"Hagos","sequence":"first","affiliation":[{"name":"Centre for Evolution and Cancer and Division of Molecular Pathology The Institute of Cancer Research  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayse U.","family":"Akarca","sequence":"additional","affiliation":[{"name":"Cancer Institute University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Ramsay","sequence":"additional","affiliation":[{"name":"Department of Histopathology University College Hospitals London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo L.","family":"Rossi","sequence":"additional","affiliation":[{"name":"Bioinformatics Istituto Nazionale Genetica Molecolare  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Pomplun","sequence":"additional","affiliation":[{"name":"Department of Histopathology University College Hospitals London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Ngai","sequence":"additional","affiliation":[{"name":"Cancer Institute University College London  London UK"},{"name":"Department of Histopathology University College Hospitals London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Moioli","sequence":"additional","affiliation":[{"name":"Hematology Unit Ospedale Papa Giovanni XXIII  Bergamo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Gianatti","sequence":"additional","affiliation":[{"name":"Pathology Unit Ospedale Papa Giovanni XXIII  Bergamo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Mcnamara","sequence":"additional","affiliation":[{"name":"Department of Haematology University College London Hospital  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Rambaldi","sequence":"additional","affiliation":[{"name":"Hematology Unit Ospedale Papa Giovanni XXIII  Bergamo Italy"},{"name":"Department of Oncology and Hematology\u2010Oncology University of Milan  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio A.","family":"Quezada","sequence":"additional","affiliation":[{"name":"Cancer Immunology Unit University College London Cancer Institute University College London  London UK"},{"name":"Research Department of Haematology University College London Cancer Institute University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Linch","sequence":"additional","affiliation":[{"name":"Research Department of Haematology University College London Cancer Institute University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Gritti","sequence":"additional","affiliation":[{"name":"Hematology Unit Ospedale Papa Giovanni XXIII  Bergamo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinyin","family":"Yuan","sequence":"additional","affiliation":[{"name":"Centre for Evolution and Cancer and Division of Molecular Pathology The Institute of Cancer Research  London UK"},{"name":"Centre for Molecular Pathology Royal Marsden Hospital  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Marafioti","sequence":"additional","affiliation":[{"name":"Cancer Institute University College London  London UK"},{"name":"Department 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